Immunotherapy in patients with non-small cell lung cancer with ECOG PS 2.

Immunotherapy is a new and very promising method of anti-cancer treatment. Unfortunately, not every patient can benefit from this treatment. The Polish drug program determines the selection of patients based on PD-L1 expression and the performance status assessed with the use of Eastern Cooperative Oncology Group Performance Status (ECOG PS) score. Patients with ECOG PS 2 represent a significant proportion of the cancer population, one which is overlooked in most clinical trials of immunotherapy. Often, a reduced performance status is the only factor that excludes the patient from treatment with immunotherapy. Choosing the optimal method of treatment in patients with a worse general condition and with multiple diseases may be a significant problem for the doctor. Assessment of performance status may be a particular problem because not every patient has a worse PS score for the same reasons. In this study, we analyse the results of treatment of patients with a poorer performance status to date, and we present tools that improve the precise assessment of the degree of the performance status, which may enable more patients to access novel lung cancer treatments.

ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases.

ATP12A encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating the composition and properties of the fluid and mucus lining the respiratory epithelia, which are essential to maintain the airway host defense and the respiratory health. Increased expression and activity of ATP12A in combination with the loss of other balancing activities, such as the bicarbonate secretion mediated by CFTR, leads to excessive acidification of the airway surface liquid and mucus dysfunction, processes that play relevant roles in the pathogenesis of cystic fibrosis and other chronic inflammatory respiratory disorders. In this review, we summarize the findings dealing with ATP12A expression, function, and modulation in the airways, which led to the consideration of ATP12A as a potential therapeutic target for the treatment of cystic fibrosis and other airway diseases; we also highlight the current advances and gaps regarding the development of therapeutic strategies aimed at ATP12A inhibition.

Genome-engineering technologies for modeling and treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by defects in the CF transmembrane conductance regulator (CFTR) protein. Due to the genetic nature of the disease, interventions in the genome can target any underlying alterations and potentially provide permanent disease resolution. The current development of gene-editing tools, such as designer nuclease technology capable of genome correction, holds great promise for both CF and other genetic diseases. In recent years, Cas9-based technologies have enabled the generation of genetically defined human stem cell and disease models based on induced pluripotent stem cells (iPSC). In this article, we outline the potential and possibilities of using CRISPR/Cas9-based gene-editing technology in CF modeling.

Generation of an induced pluripotent stem cell line (IGGi002A) from nasal cells of a cystic fibrosis patient homozygous for the G542X-CFTR mutation.

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel defective in cystic fibrosis (CF). Several CFTR mutations are causative of CF, among which G542X is a nonsense mutation introducing a premature stop codon which prevents CFTR protein synthesis. We generated a new iPSC line from nasal cells carrying G542X homozygous mutation for CFTR: IGGi002A. This cell line has normal female karyotype, express pluripotency markers and could differentiate into three germ layers in vitro. This iPSC line may be used for disease modeling (cell differentiation and organoid formation) and development of personalized treatments by genome editing or pharmacological screening.

Impact of COVID-19 in Patients with Lung Cancer: A Descriptive Analysis.

The COVID-19 pandemic poses a challenge to health systems worldwide. Limiting healthcare availability may delay early diagnosis and worsen the treatment effects of various diseases, including oncological diseases. We analyzed patients presenting to the 2nd Department of Lung Diseases and Tuberculosis in Bialystok, Poland, with suspicion of lung cancer 12 months prior to the COVID-19 pandemic (pre-COVID-19) and, similarly, 12 months after the outbreak of the pandemic (mid-COVID). In total, 320 patients were analyzed-132 prior to and 188 after the COVID-19 outbreak. During the COVID-19 period, there was a lower percentage of patients presenting with ECOG performance status 0-1, with a noticeably increased percentage of patients with ECOG PS ≥2. The disease's clinical stage (CS) was higher on admission during COVID-19. We observed more use of immunotherapy and more deaths before the start of treatment during the COVID-19 period. These results provide insight into the early effects of the COVID-19 pandemic on lung cancer patients and underscore the importance of conducting further studies to assess the long-term effects of the COVID-19 pandemic on this population.

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin.

BACKGROUND Atezolizumab is an immune checkpoint inhibitor used as first-line treatment with carboplatin and etoposide chemotherapy for advanced small cell lung cancer. Immunochemotherapy treatment decisions can be affected by patients' physical ability. Because of the exclusion of patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 from clinical trials, treatment outcome evidence in this group is limited. CASE REPORT We present the case of a 75-year-old woman with an ECOG PS of 2 admitted with respiratory symptoms and diagnosed with advanced small-cell lung cancer. After managing exacerbation of COPD and decompensated heart failure, atezolizumab with carboplatin and etoposide was administered. After 2 cycles of immunochemotherapy, deterioration of health was observed, including anemia and thrombocytopenia. Because of the good response in imaging tests and restored balance of the patient condition, immunochemotherapy was continued. After 4 cycles of combined treatment, complete regression was achieved. No another adverse effects were observed. The patient was qualified for maintenance therapy with atezolizumab. In follow-up CT scan after 2 cycles of atezolizumab, progression was observed and patient was qualified for second-line treatment. CONCLUSIONS This report presents the case of an older patient with advanced small cell lung cancer and an ECOG status of 2 who responded to combined immunochemotherapy with atezolizumab, etoposide, and carboplatin. Adverse effects observed during immunotherapy were not a reason for discontinuation of the therapy. The assessment of the effectiveness of immunotherapy in patients with ECOG PS ³2 is difficult owing to the insufficient representation of this group in clinical trials.

The Many Faces of Immune Checkpoint Inhibitor-Associated Pneumonitis: 4 Case Reports.

BACKGROUND Advanced non-small cell lung cancer has poor prognosis and low survival. Immunotherapy with the use of immune checkpoint inhibitors is a relatively new method of treatment that offers a chance to significantly extend the survival and quality of life of patients over that obtained with conventional chemotherapy. One of the complications of immunotherapy is immune checkpoint inhibitor-related pneumonitis. CASE REPORT We analyzed the available medical data on the treatment of 22 patients with non-small cell lung cancer who were treated in our clinic and qualified for immunotherapy with one of the anti-PD-1/anti-PD-L1 agents: nivolumab, atezolizumab, or pembrolizumab. In this group of patients treated with immune checkpoint inhibitors, 4 patients experienced immune checkpoint inhibitor-related pneumonitis. CONCLUSIONS Immune checkpoint inhibitor-related pneumonitis is a rare but potentially life-threatening complication of immune therapy. It can manifest in many ways, from asymptomatic to severe cases, which require quick action and treatment. Knowing the spectrum of symptoms and being alert to the possibility of such a complication is an important skill for doctors who use immunotherapy in their patients.

Self-management and integrated pulmonary care as an essential part of treatment of patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common, chronic and progressive disease that is a major public health problem worldwide. Treatment for stable COPD relies on pharmacological and non-pharmacological procedures. Education, self-management interventions and personalized pulmonary rehabilitation should be part of chronic care for patients with COPD at all stages of their disease. The comprehensive care should be provided by integrated pulmonary care based on pulmonary centers and a multidisciplinary team to all patients with COPD. Holistic approach to the patient with COPD and his involvement in therapy and working closely with healthcare professionals will improve quality of life of COPD patients. It also modifies the course of the disease, prevents progression and may reduce the frequency of exacerbations. In this article, we present the proposed model of integrated pulmonary care, structures necessary for multidisciplinary treatment and self-management intervention as essential elements in the treatment of patients with COPD.