Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study.

BACKGROUND: Targeted inhibition of the PD-L1-PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC). METHODS: CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing. FINDINGS: Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6-7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5-43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7-25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37-0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group. INTERPRETATION: Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC. FUNDING: F Hoffmann-La Roche and Genentech.

AROME-ESO Oncology Consensus Conference: access to cancer care innovations in countries with limited resources. Association of Radiotherapy and Oncology of the Mediterranean Area (AROME-Paris) and European School of Oncology (ESO - Milan).

PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.

Impact of inhalation therapy on the incidence of carious lesions in patients with asthma and COPD.

OBJECTIVE: The aim of this study was to investigate the incidence of carious lesions, the amount of salivary flow rate and pH value in patients with asthma and chronic obstructive pulmonary diseases (COPD), using inhalation therapy. The obtained results were compared with the results of adult healthy subjects, forming a control group. MATERIAL AND METHODS: The study included 80 participants aging between 18 and 65 years. The experimental group (EG) was comprised of 40 participants, previously diagnosed with asthma or COPD undergoing inhalation therapy for more than five years. The control group (CG), comprised of 40 participants, mirrored the same age and gender status of the EG. Dental status was determined by decayed, missing, and filled teeth (DMFT index). Quantity and pH value of saliva were determined in the laboratory. RESULTS: In the EG, the mean value of the salivary flow rate and pH value were statistically significantly lower than in the CG (p<0.001). Patients in the EG had a higher value of DMFT index when compared with the CG, although the difference was not statistically significant (p=0.199). Mean number of decayed teeth, as well as missing teeth, in the EG was statistically significantly higher than in the CG (p<0.001). Mean number of filled teeth in the EG was statistically significantly lower than in the CG (p<0.001). CONCLUSION: It was found that patients undergoing inhalation therapy face increasing risk of dental caries due to the lower salivary flow rate and pH value along with the inhalation therapy. They should receive intensive preventive care, including oral hygiene instruction and dietary advice.

Paraneoplastic dermatomyositis associated with adenocarcinoma of the lung.

The association of dermatomyositis and lung cancer has been recognized a long time ago. The case of a 57-year old patient with lung adenocarcinoma and dermatomyositis as the first sign of the illness is presented. The occurrence of dermatomyositis should be considered as a potential presentation of paraneoplastic syndromes, particularly in patients at risk for lung cancer.

Defense mechanisms of the respiratory system and aerosol production systems.

Aerosolized therapies have been used in everyday clinical practice for decades. Experimentation with different delivery systems have led to the creation of aerosolized insulin, antibiotics, gene therapy and chemotherapy. Several of these therapies are already clinically available while others are being investigated in active clinical trials. The main factors affecting the efficiency and safety of the aerosolized therapies are the production of the aerosol, distribution/deposition of the aerosol throughout the lung parenchyma, respiratory defense mechanisms and tissue/pharmaceutical molecule interactions. Current methods of aerosol production and distribution will be presented along with an overview of the respiratory defense mechanisms. In addition, methods of aerosol evaluation in conjunction with a future perspective of the potential development of aerosol therapies will be presented.

Pneumothorax: from definition to diagnosis and treatment.

Pneumothorax is an urgent situation that has to be treated immediately upon diagnosis. Pneumothorax is divided to primary and secondary. A primary pneumothorax is considered the one that occurs without an apparent cause and in the absence of significant lung disease. On the other hand secondary pneumothorax occurs in the presence of existing lung pathology. There is the case where an amount of air in the chest increases markedly and a one-way valve is formed leading to a tension pneumothorax. Unless reversed by effective treatment, this situation can progress and cause death. Pneumothorax can be caused by physical trauma to the chest or as a complication of medical or surgical intervention (biopsy). Symptoms typically include chest pain and shortness of breath. Diagnosis of a pneumothorax requires a chest X-ray or computed tomography (CT) scan. Small spontaneous pneumothoraces typically resolve without treatment and require only monitoring. In our current special issue we will present the definition, diagnosis and treatment of pneumothorax from different experts in the field, different countries and present different methods of treatment.

Clinical trials in advanced stage lung cancer: a survey of patients' opinion about their treatment.

BACKGROUND: The major aim of this study was to investigate what patients with advanced stage lung cancer, enrolled in a clinical trial, thought about their treatment. We also wanted to investigate if there exist any characteristics that could influence patients' opinion about the clinical trial. PATIENTS AND METHODS: Over the period from June 2008 to June 2009, 59 eligible patients were enrolled in this study. The major inclusion criteria were: participation in a clinical trial, previously treated advanced stage lung cancer, and good performance status (ECOG 0-2). All patients were asked to answer a questionnaire designed to investigate their impressions about participation in a clinical trial. The questionnaire was deposited in a sealed box which was opened at the end of the study.We investigated a possible influence of age, gender, education, lung cancer stage, chemotherapy line and tumor type on the patients' opinion about some aspects of the clinical trial. RESULTS: The majority of the patients were aware they were participating in the clinical trial and a significant number of them were very satisfied with the treatment. Of the investigated factors, only the level of education had a statistically significant influence on some of the questions raised in the questionnaire. CONCLUSIONS: Patients participating in clinical trials are satisfied with their treatment, ready to proceed with it and would recommend it to other patients. It depends mainly on health professionals to maintain this level of confidence and justify their trust.

Clinical risk factors for early complications after high-dose-rate endobronchial brachytherapy in the palliative treatment of lung cancer.

PURPOSE: This study sought to identify the rate of complications and clinical risk factors for early complications of high-dose-rate endobronchial brachytherapy (HDR-EBBT). The identification of these risk factors could result in a decrease or avoidance of complications. PATIENTS AND METHODS: We analyzed risk factors for complications in 761 patients with advanced-stage lung cancer who were treated with HDR-EBBT as a part of the multimodality therapy. We reviewed patient, radiology, and bronchology charts for complications of HDR-EBBT. Complications were defined as severe hypoxemia, global respiratory failure, cardiac arrhythmia requiring additional treatment, hemoptysis, pneumothorax, pneumomediastinum, pulmonary edema, tracheoesophageal fistulae, and death. Risk factors were defined as acute myocardial infarction > or = 6 months previously, stabilized hypertension, arrhythmia, chronic obstructive pulmonary disease (COPD), stabilized cardiomyopathy, previous external-beam radiation therapy, chemotherapy, and interventional pulmonology treatment. Age, sex, tumor histology, and tumor localization were also subjected to multivariate analyses. RESULTS: The rate of complications was 5.4%. Statistically significant (P = .001) risk factors for complications of HDR-EBBT included stabilized hypertension, controlled chronic cardiac arrhythmias, COPD, and stabilized cardiomyopathy. We found a significant correlation between age and number of risk factors, and the occurrence of complications (P = .001). CONCLUSION: Our results indicate that closer monitoring of patients with identified risk factors is advisable. Such monitoring should be performed both before and after treatment, to avoid complications.

[Frequency and relevance of concomitant diseases in elderly patients hospitalized for community acquired pneumonia].

INTRODUCTION: Patients' age and concomitant diseases are relevant for the development and treatment outcome of pneumonia. OBJECTIVE: To establish the frequency and relevance of concomitant diseases in patients over 65 years of age hospitalized for community acquired pneumonia. METHODS: The research included 550 patients hospitalized at the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica due to community acquired pneumonia. Data on concomitant diseases and mortality rate was correlated with the patients' age limit of 65 years, and then statistically analyzed and presented in tables. RESULTS: There were 446 (81.45%) patients under and 102 (18.55%) over the age of 65 years. Dyspnea, impaired consciousness, cyanosis, tachycardia and arterial hypertension were significantly more common in patients over 65 years of age, who also had a higher prognostic score. Mortality was significantly higher (21.6% vs. 6.0%) in the patients aged over 65 years (p < 0.001). Concomitant diseases were significantly more common (p < 0.001) among the patients over 65 years (94.1% vs. 69.2%), and the majority of the elderly patients had two or three comorbidities. The following comorbidities were significantly more common among the patients aged over 65 years: chronic obstructive disease, bronchiectasis, compensated and decompensated cardiomyopathy, cardiac arrhythmia, arterial hypertension and diabetes mellitus. The higher number of concomitant diseases was associated with a significantly elevated hospital mortality (p < 0.001). A statistically significant mortality rate difference was found in both age groups regarding the comorbidity of chronic obstructive disease and decompensated cardiomyopathy. CONCLUSION: The patients aged over 65 years hospitalized due to community acquired pneumonia had a statistically significantly higher prognostic score, mortality rate and concomitant diseases than the patients below 65 yeas of age. Most subjects of the older group of patients had two or three comorbidities. Concomitant diseases resulted in a statistically significant hospital mortality elevation. When comborbitities involved chronic obstructive pulmonary disease and decompensated cardiomyopathy, a statistically significant mortality difference was registered in both age groups.

[Influence of dexamethasone on appetite and body weight in lung cancer patients].

INTRODUCTION: Anorexia and cachexia are the most common symptoms in cancer patients. They increase morbidity and mortality among cancer patients as well as complications of surgery, radiotherapy and chemotherapy. The most common drugs for treatment of cancer cachexia are corticosteroids and megestrol acetate. MATERIAL AND METHODS: The purpose of this study was to determine the influence of dexamethasone on appetite loss and weight loss in lung cancer patients treated with chemotherapy. Group A (30 patients) was treated with cisplatin, etoposide and standard supportive therapy, while group B (30 patients) received, in addition to this treatment, dexamethasone in the dose of 8 mg intravenously per day (1-3 day of chemotherapy). RESULTS: There was a statistically significant difference in appetite loss between two groups after the second chemotherapy cycle favouring group A. The analysis of weight loss showed a statistically significant difference between two groups after both chemotherapy cycles, once again in favour of group A. Concerning the impovement of appetite and weight gain, there was no statistically significant difference between two groups after both chemotherapy cycles. DISCUSSION: Many double-blind randomized controlled studies showed beneficial symptomatic effect of corticosteroids in cancer cachexia, especially on the improvement of appetite, food intake and performance status. In most of the studies the weight gain was not recorded The most effective type of corticosteroids, dose and route of administration have not been established. CONCLUSION: Dexamethasone significantly decreases appetite loss and weight loss in lung cancer patients treated with chemotherapy, while it has no influence on appetite impovement and weight gain.