The aim of the SYRMA-CT collaboration is to set-up the first clinical trial of phase-contrast breast CT with synchrotron radiation (SR). In order to combine high image quality and low delivered dose ...a number of innovative elements are merged: a CdTe single photon counting detector, state-of-the-art CT reconstruction and phase retrieval algorithms. To facilitate an accurate exam optimization, a Monte Carlo model was developed for dose calculation using GEANT4. In this study, high isotropic spatial resolution (120 μm)(3) CT scans of objects with dimensions and attenuation similar to a human breast were acquired, delivering mean glandular doses in the range of those delivered in clinical breast CT (5-25 mGy). Due to the spatial coherence of the SR beam and the long distance between sample and detector, the images contain, not only absorption, but also phase information from the samples. The application of a phase-retrieval procedure increases the contrast-to-noise ratio of the tomographic images, while the contrast remains almost constant. After applying the simultaneous algebraic reconstruction technique to low-dose phase-retrieved data sets (about 5 mGy) with a reduced number of projections, the spatial resolution was found to be equal to filtered back projection utilizing a four fold higher dose, while the contrast-to-noise ratio was reduced by 30%. These first results indicate the feasibility of clinical breast CT with SR.
Introduction
Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical ...de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC).
Materials and methods
1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS).
Results
27.5% of patients with ILC had ≥ 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (
p
= 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15–19.5
p
= 0.03), T3–T4 tumors (OR = 4.93, 95% CI 1.10–22.2,
p
= 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16–6.50,
p
= 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77–3.41,
p
= 0.20).
Conclusions
ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies.
Benign thyroid nodules are an extremely common occurrence. Radiofrequency ablation (RFA) is gaining ground as an effective technique for their treatment, in case they become symptomatic. Here we ...review what are the current indications to RFA, its outcomes in terms of efficacy, tolerability, and cost, and also how it compares to the other conventional and experimental treatment modalities for benign thyroid nodules. Moreover, we will also address the issue of treating with this technique patients with cardiac pacemakers (PM) or implantable cardioverter-defibrillators (ICD), as it is a rather frequent occurrence that has never been addressed in detail in the literature.
The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra ...Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still ...represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.
Highlights • Specific growth factors were observed in sera of asbestos exposed workers. • The chemokines IP-10 and RANTES were associated with the severity of diseases. • RANTES showed the highest ...serum level. • RANTES showed a significant relationship between sera and pleural effusions. • Mesothelioma biopsies showed detectable levels for RANTES, VEGF, and IP-10.
Purpose
Monitoring mutation status in circulating free DNA (cfDNA) during target therapy could hold significant clinical importance in non-small cell lung cancer (NSCLC). Our aim is to establish if ...EGFR mutational status change on cfDNA has predictive value that can impact clinical management of NSCLC patients care.
Methods
This study included 30 patients with EGFR-mutated NSCLC. Blood samples were collected at diagnosis (T0) and in 19 patients during therapy (T1).
Results
Concordance between T0 and T1 EGFR mutation status for patients evaluable for both samples (
n
= 19) was 79%, with a sensitivity of 100% (95% CI: 55.5–100.0) and specificity of 60.0% (95% CI: 26.2–86.8). For the patients in oncological therapy with targeted drug and with T1 sample available (
n
= 18), survival outcomes were evaluated. For both mutation-negative T0 and T1 patients, 12-month progression-free survival (PFS) was 66.7% (95% CI: 27.2–100.0) and 12-month overall survival (OS) was 100% (95% CI: 1.00–1.00); for patients mutated both at T0 and T1, PFS was 22.2% (95% CI: 6.5–75.4%) and OS was 55.6% (95% CI: 20.4–96.1%).
Conclusion
EGFR mutation status can be assessed using cfDNA for routine purposes and longitudinal assessment of plasma mutation is an easy approach to monitor the therapeutic response or resistance onset.
Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a ...consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment.
We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS).
A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement.
The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68–0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87–1.12; P = 0.84).
This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.
•Adjuvant endocrine therapy reduces the risk of recurrence and increases survival rates in breast cancer patients.•The benefit of extended adjuvant endocrine therapy with aromatase inhibitors (AIs) is currently being debated.•Our retrospective analysis of 8 randomized clinical trials provides evidence of a disease free survival (DFS) benefit with extended adjuvant AIs therapy.•DFS benefit was higher in patients with positive nodal status.•Identification of new biomarkers could help identify specific subgroups of patients able to benefit from extended adjuvant endocrine therapy with AIs.
The thickening of the vessel wall (intimal hyperplasia) is a pathological process which often follows revascularization approaches such as transluminal angioplasty and artery bypass graft, procedures ...used to re-vascularize stenotic artery. Despite the significant improvements in the treatment of intimal hyperplasia obtained in the last years, the problem has not completely solved. Nucleic acid based-drugs (NABDs) represent an emergent class of molecules with potential therapeutic value for the treatment of intimal hyperplasia. NABDs of interest in the field of intimal hyperplasia are: ribozymes, DNAzymes, antisense oligonucleotides, decoy oligonucleotides, small interfering RNAs and micro interfering RNAs. These molecules can recognize, in a sequencespecific fashion, a target which, depending on the different NABDs, can be represented by a nucleic acid or a protein. Upon binding, NABDs can down-modulate the functions of the target (mRNA/proteins) and thus they are used to impair the functions of disease-causing biological molecules.In spite of the great therapeutic potential demonstrated by NABDs in many experimental model of intima hyperplasia, their practical use is hindered by the necessity to identify optimal delivery systems to the vasculature. In the first part of this review a brief description of the clinical problem related to intima hyperplasia formation after revascularization procedures is reported. In the second part, the attention is focused on the experimental evidences of NABD therapeutic potential in the prevention of intimal hyperplasia. Finally, in the third part, we will describe the strategies developed to optimize NABD delivery to the diseased vessel.
PDF
