508 research outputs found
Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy
The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance. After a thorough literature review, STK11 mutations condition the prognosis of NSCLC patients receiving ICI-containing regimens, implying a relevant biological and clinical significance. On the other hand, waiting for prospective and solid data, the putative negative predictive value of STK11 inactivation towards IT is sustained by less evidence. The physiologic regulation of multiple cellular pathways performed by STK11 likely explains the multifaceted modifications in tumor cells, stroma, and tumor immune microenvironment (TIME) observed in STK11 mutant lung cancer, particularly explored in the molecular subgroup of KRAS co-mutation. IT approaches available thus far in NSCLC, mainly represented by anti-PD-1/PD-L1 inhibitors, are not promising in the case of STK11 inactivation. Perceptive strategies aimed at modulating the TIME, regardless of STK11 status or specifically addressed to STK11-mutated cases, will hopefully provide valid therapeutic options to be adopted in the clinical practice
Clinical Impact of COVID-19 Outbreak on Cancer Patients: A Retrospective Study
Background: Coronavirus disease (COVID-19), an acute respiratory syndrome caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread worldwide, significantly affecting the outcome of a highly vulnerable group such as cancer patients. The aim of the present study was to evaluate the clinical impact of COVID-19 infection on outcome and oncologic treatment of cancer patients. Patient and methods: We retrospectively enrolled cancer patients with laboratory and/or radiologic confirmed SARS-CoV-2 infection, admitted to our center from February to April 2020. Descriptive statistics were used to summarize the clinical data and univariate analyses were performed to investigate the impact of anticancer treatment modifications due to COVID-19 outbreak on the short-term overall survival (OS). Results: Among 61 patients enrolled, 49 (80%) were undergoing anticancer treatment and 41 (67%) had metastatic disease. Most patients were men; median age was 68 years. Median OS was 46.6 days (40% of deaths occurred within 20 days from COVID-19 diagnosis). Among 59 patients with available data on therapeutic course, 46 experienced consequences on their anticancer treatment schedule. Interruption or a starting failure of the oncologic therapy correlated with significant shorter OS. Anticancer treatment delays did not negatively affect the OS. Lymphocytopenia development after COVID was significantly associated with worst outcome. Conclusions: COVID-19 diagnosis in cancer patients may affect their short-term OS, especially in case of interruption/starting failure of cancer therapy. Maintaining/delaying cancer therapy seems not to influence the outcome in selected patients with recent COVID-19 diagnosis
Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review
Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments. Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinumâetoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinumâetoposide compared with control (p < 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed. Conclusions: Based on retrospective data available to date, platinumâetoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinumâetoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib
Dynamic evaluation of circulating mirna profile in egfrâ mutated nsclc patients treated with egfrâtkis
Background: Resistance to EGFRâTKIs constitutes a major challenge for the management of EGFRâmutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miRâ21, miRâ27a and miRâ181a) as a surrogate for predicting EGFRâTKI performance in EGFRâmutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFRâmutated NSCLC patients treated with EGFRâTKIs were collected at different points in time and miRNA levels were assessed by RTâPCR. Results: Higher basal values of miRâ21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miRâ21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFRâTKI treatment showed that patients who experienced SD had an increase in miRâ21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miRâ27a (FC = 3.1) and miRâ181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miRâ21 levels in NSCLC cells that became resistant after exposure to EGFRâTKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miRâ21, and their dynamic change over time in predicting EGFRâTKI response in EGFRâmutated NSCLC
Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients
Introduction: Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC). Methods: Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD-1+ and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (IeffS). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response. Results: High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P < 0.001), OS (P < 0.01) and ICI-response (P < 0.05). Thus, sPD-L1high, CD8+PD-1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS characterizing patients with significantly (P < 0.001) prolonged PFS (median NR vs 2.3 months) and OS (median NR vs 4.1) and greater benefit from ICIs (P < 0.01). We then combined each risk parameter composing IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes. A remarkable impact of IeffS-LIPI integration was documented on survival outcome (PFS, HR = 4.61; 95%CI = 2.32-9.18; P < 0.001; OS, HR=4.03; 95%CI=1.91-8.67; P < 0.001) and ICI-response (AUC=0.90, 95%CI=0.81-0.97, P < 0.001). Conclusion: Composite risk models based on blood parameters featuring the tumor-host interaction might provide accurate prognostic scores able to predict ICI benefit in NSCLC patients
PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors
Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association (p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype (p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required
Measurement of eta photoproduction on the proton from threshold to 1500 MeV
Beam asymmetry and differential cross section for the reaction gamma+p->eta+p
were measured from production threshold to 1500 MeV photon laboratory energy.
The two dominant neutral decay modes of the eta meson, eta->2g and eta->3pi0,
were analyzed. The full set of measurements is in good agreement with
previously published results. Our data were compared with three models. They
all fit satisfactorily the results but their respective resonance contributions
are quite different. The possible photoexcitation of a narrow state N(1670) was
investigated and no evidence was found.Comment: 18 pages, 14 figures, 4 tables Submitted to EPJ
Differential cross section measurement of eta photoproduction on the proton from threshold to 1100 MeV
The differential cross section for the reaction p(gamma, eta p) has been
measured from threshold to 1100 MeV photon laboratory energy. For the first
time, the region of the S11(1535) resonance is fully covered in a
photoproduction experiment and allows a precise extraction of its parameters at
the photon point. Above 1000 MeV, S-wave dominance vanishes while a P-wave
contribution is observed whose nature will have to be clarified. These high
precision data together with the already measured beam asymmetry data will
provide stringent constraints on the extraction of new couplings of baryon
resonances to the eta meson.Comment: 10 pages, 5 figures, submitted to Phys. Letters B. Typos corrected.
Some more information on the S11(1535) parameter
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