Tumour infiltrating lymphocytes (TILs) in breast cancer during pregnancy

Tumour infiltrating lymphocytes (TILs) is one of the most exciting breast cancer biomarkers, yet no data is available on its prevalence in tumours diagnosed during pregnancy.We evaluated the prevalence of TILs (stromal and intratumoural) in pregnant and non-pregnant young breast cancer patients.11/116 (9.6%) of the non-pregnant and 2/86 (2.3%) pregnant patients had TILs ≥ 50% (p 0.001) with highest prevalence observed in triple negative tumours (p = 0.01).This is the first report on TILs in tumours diagnosed during pregnancy. The low prevalence could reflect the state of low host immunity associated with pregnancy

Unfavorable prognostic role of tumor-infiltrating lymphocytes in hormone-receptor positive, HER2 negative metastatic breast cancer treated with metronomic chemotherapy

Abstract Background High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown. Patients and methods We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination). Results Of the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (≥10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0–4%, 5–9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011). Conclusions High TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies

Pathological features and survival outcomes of very young patients with early breast cancer: How much is "very young"?

Abstract We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: Patients aged p = 0.79) and overall survival ( p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too. In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered

Genomic and transcriptomic analyses of thyroid cancers identify DICER1 somatic mutations in adult follicular-patterned RAS-like tumors

BackgroundPapillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and BRAFV600E, RAS mutations, and gene fusions are well-established drivers. DICER1 mutations were described in specific sets of TC patients but represent a rare event in adult TC patients.MethodsHere, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA).ResultsThe occurrence of BRAFV600E (44%), RAS mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the DICER1 gene (p.D1709N and p.D1810V) were identified. DICER1 mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent DICER1 mutation (p.R459*) is also observed. Additional putative drivers include ROS1 gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that DICER1 tumors are RAS-like, whereas the ROS1-mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of DICER1 and ROS1 mutations in thyroid lesions by investigating the COSMIC database.ConclusionEven though small, our series recapitulates the genetic background of PTC. Furthermore, we identified DICER1 mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification

Status of the RFQ linac installation and conditioning of the Linear IFMIF Prototype Accelerator

Abstract The Radio Frequency Quadrupole (RFQ) linac and 1.6 MW RF power system of the Linear IFMIF Prototype Accelerator (LIPAc) facility in the International Fusion Energy Research Center (IFERC) in Rokkasho (Japan) has been installed and conditioned. During the assembly and tuning process, the RFQ cavity was protected with a temporary tent from the potential deterioration of performance caused by dust. The vacuum in the cavity was improved through the 100 °C baking process of the cavity. The high power test of the 175 MHz RF systems up to 200 kW in CW for each of the eight RF chains was performed for checking its stable output reproducibility in Japan, before connecting 9–3/16 inch coaxial transmission lines from the RF chains to the RF input couplers of the cavity. It was confirmed that the eight RF chains provided the balanced RF power to the single RFQ cavity in-phase using a feedback loop and a synchronization system. The peak power in the cavity achieved 150 kW in the pulsed mode, which corresponds approximately to the required electric field to accelerate proton beam. Such RF conditioning process is ongoing to achieve 600 kW approximately required for deuteron beam commissioning planned in 2018

Space-QUEST: Experiments with quantum entanglement in space

The European Space Agency (ESA) has supported a range of studies in the field of quantum physics and quantum information science in space for several years, and consequently we have submitted the mission proposal Space-QUEST (Quantum Entanglement for Space Experiments) to the European Life and Physical Sciences in Space Program. We propose to perform space-to-ground quantum communication tests from the International Space Station (ISS). We present the proposed experiments in space as well as the design of a space based quantum communication payload.Comment: 4 pages, 1 figure, accepted for the 59th International Astronautical Congress (IAC) 200

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Peer reviewe