Incidence of Infections and Predictors of Mortality During Checkpoint Inhibitor Immunotherapy in Patients With Advanced Lung Cancer: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized nonsmall cell lung cancer (NSCLC) treatment and significantly increased overall survival of patients. However, the incidence of concurrent infections and their management is still debated. METHODS: From August 2015 to October 2019, all consecutive patients with NSCLC who received nivolumab or pembrolizumab as first- or second-line therapy were retrospectively evaluated. At the time of analysis all patients had died. Clinical characteristics of patients, type of infections, and predictors of mortality were analyzed. RESULTS: A total of 118 patients were identified: 74 in the nivolumab group and 44 in the pembrolizumab group. At least 1 infection was recorded in 22% of the nivolumab-group versus 27% of the pembrolizumab-group (P = .178). In both groups, the main infection was pneumonia, followed by skin and soft tissue infections, urinary tract infections, and gastroenteritis. Crude mortality for first infection was 10.7%, followed by 25% and 40% for the second and third recurrence, respectively (p for trend = .146). No opportunistic infections were recorded. It is notable that, by Cox-regression model, the independent predictor of mortality was a higher Eastern Cooperative Oncology Group performance status at baseline (P < .001), whereas the multidisciplinary diagnosis and treatment of concurrent infections was associated with a reduced probability of mortality (adjusted hazard ratio = 0.50; 95% confidence interval = 0.30-0.83; P < .001). CONCLUSIONS: In patients with NSCLC treated with ICIs, multidisciplinary management of concurrent infections may reduce the risk of mortality. Further studies to investigate risk factors for infections, as well as appropriate management strategies and preventive measures in this setting, are warranted.

Smoking Prevalence, Knowledge and Perceptions on Tobacco Control Among Healthcare Professionals: A Survey in an Italian Cancer Center.

Smoking is recognized as the major cause of lung cancer. Healthcare professionals play an important role in lung cancer prevention policies, as they act as a source of guidance for patients and advocates. The following survey evaluated prevalence, knowledge, and attitudes toward tobacco smoking among a sample of workers in "IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, an Italian cancer hospital. An anonymous questionnaire was completed by 104 healthcare professionals to collect personal and occupational data about smoking status, knowledge about the harms of smoking, current legislation in place, Second-Hand Smoke (SHS) awareness, and, for ex-smokers, the reasons for quitting. Among participants, 17.8% were current smokers, 26.2% former smokers, and 56% never smoked. Only 40% acknowledged that the smoking ban is generally respected, and 63.2% reported that they smoke during working hours. Most of the participants perceived tobacco control policy as an efficient way to protect public health. Currently, the implementation of Italian anti-smoking legislation has so far improved neither smoking cessation rates nor the will to quit smoking completely. Our experience highlights that to date the anti-smoking strategies have limited efficacy even in a cancer center; in fact, there is still a large prevalence of smokers among hospital personnel. Therefore, it is strongly suggested that interventions be shared with all healthcare workers, specifically aimed at developing a culture of health promotion.

Impact of tobacco control interventions on smoking initiation, cessation, and prevalence: a systematic review.

This article investigates the effects of tobacco control policies on smoking initiation, cessation and prevalence by examining the papers published in the last 5 years. Twenty-one articles have been selected by two authors and sorted by four types of tobacco control: tobacco prices, anti-smoking campaigns for young people, mass media intervention and public smoking bans. Price/tax increase has deterrent effect on smoking initiation but does not promote smoking cessation; intervention on young people could reduce the smoking initiation if carried out at an early age and if acted on social skills and with peer-led approach, as opposed to restraining measures which hare generally easily circumvented by young people. The mass media campaigns showed positive effect on attempts to quit among smokers if carried forward over time and by involving multiple communication channels (TV, internet, radio). The bans in public have little effect on smoking cessation but could improve the overall well-being of non-smokers. Heterogeneous results have been described by different studies probably because of different research methodologies, cultural aspects and the really effective implementation of the rules for each country. In conclusion, comprehensive tobacco control interventions to reduce smoking prevalence and modify the smoking behavior are recommended. Moreover, the use of e-cigarettes and heat-not-burn (HnB) products, as possible helping tool for smoke cessation, currently remains controversial.

EPSILoN: A Prognostic Score Using Clinical and Blood Biomarkers in Advanced Non-Small-cell Lung Cancer Treated With Immunotherapy.

BACKGROUND: Second-line immunotherapy (IO) has shown an overall survival benefit. However, only 18% to 20% of patients with advanced non-small-cell lung cancer (aNSCLC) will respond, with a median progression-free survival (PFS) of 2 to 4 months. Thus, biomarkers to select those patients most likely to benefit from IO are greatly needed. PATIENTS AND METHODS: We conducted a retrospective analysis of 154 patients with aNSCLC who had received anti-programmed cell death 1 therapy as second line or further treatment. We assessed the absolute neutrophil, lymphocyte, monocyte, and eosinophil counts at baseline (T0) and the second (T1) and third (T2) cycles. The neutrophil/lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte/monocyte ratio (LMR), and their percentage of change at T1 and T2 compared with T0 were evaluated. The clinical characteristics and lactate dehydrogenase (LDH) level were also considered. Univariate and multivariate analyses were performed. Significant biomarkers for PFS on multivariate analysis were combined in a prognostic score. RESULTS: For overall survival, the negative prognostic biomarkers were Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, NLR at T0, and dNLR at T1; the LMR at T0, T1, and T2 was identified as a positive prognostic biomarker. For PFS, the negative prognostic biomarkers were ECOG PS 2, liver metastases, NLR at T0, dNLR at T1 and T2, and ≥ 30% increase of NLR from T0 to T1; the positive prognostic biomarkers were heavy smoking, LDH, and LMR at T2. The ≥ 30% increase of LMR from T0 to T1 and T0 to T2 correlated with the overall response rate. A prognostic score (EPSILoN score; smoking, ECOG PS, liver metastases, LDH, NLR) identified 3 prognostic groups (median PFS, 10.2, 4.9, and 1.7 months, respectively; P < .001). CONCLUSIONS: The EPSILoN score combines 5 baseline clinical and blood biomarkers and can help to identify patients with aNSCLC who will most likely benefit from second-line IO. Further studies are warranted.

Tobacco control in Europe: A review of campaign strategies for teenagers and adults.

BACKGROUND: In Europe the prevalence of tobacco use in adults and adolescents is among the highest within the WHO regions. Many resources have been allocated toward the prevention and support for smoking cessation. However, the implemented strategies in Europe have not been systematically evaluated. METHODS: A systematic literature review was carried out to identify studies that analyzed the efficacy of the main smoking-prevention campaigns conducted in Europe. PRISMA guidelines were used to systematically review and extract data. RESULTS: A total of 24 studies meeting inclusion criteria were identified. Each article was thoroughly reviewed and evaluated for quality, design, and methodology, with reference to the main areas of intervention: school (8); mass media (4) and technological tools (4); smoke-free environments (3); packaging (2) and taxes (3). The school programmes focusing on building skills to recognize and resist negative influences, the intensive use of media and technological equipments, health warnings and excise taxes have showed to be effective tools in reducing the tobacco use. CONCLUSIONS: Intervention programmes to implement tobacco control policies and smoking cessation are active in many European countries. However, these programmes need to be constantly sustained to achieve a long term efficacy.

Pulmonary alveolar microlithiasis. World cases and review of the literature.

Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic disease with unknown etiology and pathogenesis. The present work updates the world literature on PAM up to the end of 2001 by means of a full review, including minor reports in local languages (not English). Excluding secondary cases, a total of 424 cases have been reported worldwide, 269 of which were sporadic and showed a prevalence of the male sex and 155 of which were familial cases and prevalently affected the female sex. The highest number of cases has been reported in Europe, followed by Asia, especially Asia Minor, while the single nations with the greatest number of reported cases are Turkey, then Italy and the USA. The salient clinical features of PAM as described in the literature are analyzed: family history, clinical course, association with other diseases, presence of calcification in other organs. In the first cases, reported in the 60s and 70s, diagnosis was primarily made at autopsy, whereas nowadays diagnostic investigation is made above all by transbronchial biopsy and bronchoalveolar lavage. Radiological imaging is sufficient in cases where other family members are known to be affected, diagnosed by means of invasive techniques. There is no known treatment to date, while lung transplantation is performed in the severest cases. A better knowledge of the epidemiological characteristics of this rare disease could help to diagnose a larger number of cases and to gain insight into its etiology and pathogenesis, which are still unknown.

[Pulmonary alveolar microlithiasis: clinical and radiological course of three cases according to conventional radiology and HRCT. A hypothesis for radiological classification].

Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease of unknown etiology and pathogenesis. The disease is characterized by the diffuse presence in the alveoli of minute calcific deposits known as microliths. In most cases patients have mild clinical symptoms, contrasting with the severe radiographic appearance: this is a typical feature that should raise the suspicion of PAM. The first to describe the clinical and radiographic aspects of the disease, as well as the first case series, was the radiologist Sosman. In recent years, high resolution computed tomography (HRCT) has made it possible to define the extent and severity of the disease more precisely, and has demonstrated calcifications in anatomical sites that could not be shown by conventional radiology. The present paper describes the radiological evolution of the disease, and suggests a classification based on the radiographic and HRCT follow-up of the three clinical cases: two young patients followed up for 24 and 11 years and one elderly man who is still alive and is the PAM case with the longest survival since diagnosis, over 50 years, to be reported in the international literature.