Osimertinib-induced Cardiac Dysfunction in EGFR-Mutated Lung Cancer: A Case Series of Five Patients

Introduction: The gold standard treatment for Epidermal Growth Factor Receptor (EGFR) positive Non-Small Cell Lung Cancer (NSCLC)patients is represented byosimertinib, an irreversible third-generation EGFR inhibitor that has been providingimportant outcomes’ improvementscompared to chemotherapy and other target therapies; either upfront or as second line therapy, in case of  EGFR T790M detection after previous tyrosine kinase inhibitors (TKI).Osimertinib is generally well tolerated. Most common side effects are diarrhea, rash, paronychia, dry skin and alsochanges in QT interval.Presentation of case series: Here we report five cases of left ventricular dysfunction duringosimertinib treatment, observed between January 2017 and August 2018. The five patients, with a general low cardiovascular risk profile, required a dose modification/discontinuation of the TKI therapy and a specific cardio-protective treatment, normally with a recovery of the systolic function.Conclusion: Both American and European compound labels highlight warnings of cardiomyopathy and changes in cardiac contractility during osimertinib treatment, recommending cardiac monitoring and dose adjustment in patients with cardiac risk factors. In spite of this, a standardized echocardiographic follow-up in the entire population is still not available and recommendations about the use of tissue Doppler echocardiography with more sophisticated indices are missing. With the expanding use of osimertinib we need better strategies to prevent or mitigate cardiovascular damage from cancer therapy in a larger multidisciplinary approach in which every issue is carefully evaluated

Performing oncological procedures during COVID-19 outbreak: a picture from an Italian cancer center

Aim: Since SARS-CoV-2 infection rapidly spread around the world, Italy has quickly become one of the most affected countries. Healthcare systems introduced strict infection control measures to ensure optimal care, especially in frail groups such as cancer patients (pts). This study investigated the efficacy of SARS-CoV-2 pre-procedure screening and whether COVID-19 influenced timely diagnosis and therapy. Methods: Data of oncological procedures of pts with confirmed or suspected cancer diagnosis, treated at Oncology Department or coming from Emergency Department of San Luigi Gonzaga Hospital between June 2020 and March 2021 were retrospectively collected. A nasopharyngeal swab (NPS) was performed in outpatients 24/48 h before procedures. Inpatients were tested by NPS before and after hospitalization. Results: Two hundred and twenty-one pts were included in this analysis. Median age was 73 years, males were 58%. Eastern Cooperative Oncology Group (ECOG) Performance Status was 0 or 1 in 88% of pts. The most frequent cancer type was lung cancer (57%). Stages IV were 77%. Two hundred and forty-three scheduled procedures were performed with diagnostic (n: 142; 58%), therapeutic (n: 55; 23%), and palliative (n: 46; 19%) intent. One hundred and four and 139 procedures were performed in out- and in-pts, respectively. Of the 234 NPS performed, 10 (4%) were positive. Two pts were infected during hospitalization, 8 in community. Most of them were asymptomatic, while only 2 had mild symptoms. Eight procedures (3%) were postponed, 1 cancelled, while 2 were performed in positive pts. Median time to resolution of the infection was 17 days (11–36). Median delay in the procedures was 25 days (14–55). Five pts started systemic treatment, after a median time of 37.5 days (13–57). Conclusions: SARS-CoV-2 infection led to the postponement of a small, but not negligible percentage of oncological procedures. However, the low infection rate observed suggests that structured screening for COVID-19 is critical for the best management of scheduled procedures during pandemic

Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.Fil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina ; ArgentinaFil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina ; ArgentinaFil: Tharu, Fernando. Cornell University; Estados UnidosFil: Yang, Shao Ning. Cornell University; Estados UnidosFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina ; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Amorós, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Isse, Blanca Alicia de Los Angeles G.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farias, Ricardo Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; ArgentinaFil: Ahn, Haelee. Cornell University; Estados UnidosFil: Tian, Ye F.. Cornell University; Estados UnidosFil: Tabbò, Fabrizio. Cornell University; Estados UnidosFil: Singh, Ajnesh. Cornell University; Estados UnidosFil: Inghirami, Giorgio. Cornell University; Estados UnidosFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados UnidosFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer

Background: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB). Methods: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion. Results: Of 33 patients undergoing BAL and PB sampling, 21 had histologically-confirmed LC. Most cases were locally-advanced or metastatic non-small cell LC. T cell characteristics were not significantly different in t-BAL vs. cl-BAL. Compared to PB, CD8 T cells in BAL presented features of immune activation and exhaustion (high PD-1, low IFN-g production). Accordingly, regulatory CD4 T cells were also higher in BAL vs. PB. When dichotomizing T cell density in t-BAL in high and low, we found that PD-L1 expression in LC was associated with T cell density in t-BAL. T-BAL with high T cell density had higher %IFN-g+CD8 T cells and lower %T-regs. Conclusion: In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome

REHABILITATION NEEDS AND PERSPECTIVES IN LONG-TERM LUNG CANCER SURVIVORS

Lung cancer still remains the first cause of global cancer mortality but the advent of new therapeutic strategies is profoundly changing its prognosis. New survival data announce a significant increase in lung cancer survivors in the next decades. This population may have sequelae related to treatments or chronic side effects of ongoing therapies with remarkable repercussions on their quality of life. In this context, there will be different groups of lung cancer survivors with different demands and limitations. Therefore, it becomes relevant to properly identify their needs in order to design appropriate rehabilitation programs. Multidisciplinary work is essential in order to answer to physical, mental and social needs of this new group of survivors