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One‐year survival of patients with pulmonary malignancy according to the presence of LRTI (a) () Group 1 (LRTI+), and () Group 2 (LRTI−) and solitary and multiple pathogen LRTI (b) () Multiple pathogen (LRTI+), and () Solitary pathogen (LRTI+).
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Background:
Pulmonary malignancy is one of the most frequent and fatal cancers in older patients. As data on lower respiratory tract infection (LRTI) and the outcome of lung cancer are scarce, our objective was to determine the impact of LRTI on therapeutic possibilities and one-year mortality.
Methods:
Patients undergoing bronchoscopy in 2017 w...
Citations
... On the other hand, emerging evidence has shown that respiratory tumor cells could secrete immunosuppressive factors, which will inhibit the normal natural barrier function of the respiratory tract. Ultimately, lung cancer patients are more susceptible to co-infection compared to other tumor patients due to increased alveolar and bronchial secretions, as well as bronchial mass obstruction [28,29]. ...
Background
Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients.
Methods
This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.
Results
A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3–4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04–18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11–6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21–5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22–4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03–6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit.
Conclusions
Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.
... This may be related to the incidence of these neoplasms [23] . Meanwhile, lung cancer patients in ltrate and continuously secrete immunosuppressive factors by respiratory tumor cells, and the body's natural barrier function is inhibited, resulting in increased alveoli and bronchial secretions and mass obstruction of bronchi making lung cancer patients more susceptible to co-infection than non-lung cancer patients [24,25] . ...
(1) Background
Patients with malignancy are more vulnerable to developing nosocomial infections. Limited studies investigated cancer patients' clinical features and prognostic factors of fungi infections. Herein, this study was performed to explore the clinical characteristics of nosocomial infections due to fungi and develop a nomogram to predict the in-hospital death risk of these patients.
(2) Methods: This retrospective observational study analyzed cancer patients with nosocomial infections caused by fungi from September 2013 to September 2021. The univariate and multivariate logistics regression analyses were utilized to identify the influencing factors of in-hospital death risk of nosocomial infections caused by fungi. A nomogram was developed to predict the in-hospital death risk of these individuals, with the receiver operating characteristics curve (ROC), calibration curve, and decision curve being generated to evaluate its performance.
(3) Results: 216 patients with solid tumors developed fungal infections during hospitalization, of which 57 experienced in-hospital death. C.albicans is the most common fungal species(68.0%). The respiratory system was the most common site of infection(59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that ECOG-PS 3–4, pulmonary metastases, thrombocytopenia, hypoalbuminemia, and mechanical ventilation were independent risk factors of in-hospital death risk. A nomogram was constructed based on the identified risk factors to predict the in-hospital death risk of these patients.
(4) Conclusions: Fungi-related nosocomial infections are common in solid tumors and have a bleak prognosis. The constructed nomogram could help oncologists make a timely and appropriate clinical decision with significant net clinical benefit to patients.
... The presence of inflammatory processes in mNSCLC patients may be related to the presence of malignancy itself, to concomitant smoke-associated bronchopulmonary chronic disease and to the presence of relapsing bacterial infections related to incomplete integrity the airways (44)(45)(46)(47)(48)(49). ...
Peripheral-immune-checkpoint blockade (P-ICB) with mAbs to PD-1 (nivolumab and pembrolizumab) or PD-L1 (atezolizumab, durvalumab, avelumab) alone or combination with chemotherapy represents a novel active treatment for mNSCLC patients. However, this therapy can be associated to immune-related adverse events (irAEs) and high cost. Therefore, finding reliable biomarkers of response and irAEs is strongly encouraged to accurately select patients who may potentially benefit from the immuno-oncological treatment. This is a retrospective multi-institutional analysis performed on ninety-five mNSCLC patients who received real-world salvage therapy with nivolumab or atezolizumab between December 2015 and April 2020. The outcome of these patients in term of PFS and OS was evaluated in comparison with different serum levels of C-reactive protein (CRP), Erythrocyte Sedimention Rate (ESR) and Procalcitonin (PCT) by performing Kaplan–Meier and Log-rank test and multivariate analysis. We found that high baseline levels of CRP, ESR, and PCT were strongly predictive of poor outcome (P <0.05) with the worse prognosis detected in those patients with a baseline levels of both ESR and PCT over the pre-established cut off (median OS recorded in patients with no marker over the cut off vs. those with just one marker over the cut off vs. those with both markers over the cut off: 40 ± 59 vs. 15.5 ± 5.5 vs. 5.5 ± 1.6 months, respectively; P <0.0001). Our results suggest the predictive value of systemic inflammation and suggest a potential role of PCT in predicting a poor outcome in mNSCLC receiving PD-1/PD-L1 blocking mAbs. This finding also suggests a potential role of subclinical bacterial infections in defining the response to PD-1/PD-L1 blocking mAbs that deserves further and more specific investigations.
... Concomitant lung diseases (eg, chronic obstructive lung disease, emphysema, ILDs, lung infections) are often delaying or complicating diagnosis and/or treatment. 9 As LC is often associated with reduced survival and ILDs are frequently progressive with shorter life expectancy, our aim was to analyze LC patients in our Hungarian ILD cohort. Therapeutic possibilities and outcome were analyzed in both sexes. ...
... 20 The majority of our patients already had metastatic disease, also in line with previous observations, as diagnosis is often late and a significant proportion of the patients did not meet the criteria to receive combined chemotherapy. 9 Activating mutations in the EGFR gene was detected in only one case, and 62% of the patients showed EGFR/KRAS wild phenotype while PD-L1 > 1% expression was found in three cases. In Hungary, KRAS testing is routinely performed due to special reimbursement issues. ...
Background
Fibrosing interstitial lung diseases (ILDs) are associated with poor survival and an increased risk of developing lung cancer (LC). Patient and LC characteristics, therapeutic possibilities and survival in this rare patient population are not well established.
Methods
Fibrosing ILD patients treated at the Department of Pulmonology Semmelweis University were reviewed retrospectively between 2012–2018 (N = 160). All patients with concomitant LC (N = 23) underwent detailed pulmonary evaluation. Cancer characteristics including driver mutation data, as well as therapy and survival were analyzed.
Results
ILD‐LC patients (56% men, mean age 73 ± 6 years) had mild‐moderate lung functional impairment (forced vital capacity [FVC]: 80 ± 24%ref., forced expiratory volume in one second [FEV1]: 76 ± 27%ref.; transfer factor of the lung for carbon monoxide [TLCO]: 62 ± 25% reference). In 56% of cases histology confirmed adenocarcinoma followed by squamous cell carcinoma in 26%. Lobectomy could only be performed in one case; driver mutation was present in one patient. Chemotherapy was most commonly administered; however, 26% could only receive supportive palliative care. Four idiopathic pulmonary fibrosis patients received concomitant nintedanib to their LC treatment. Median survival of ILD‐LC patients was only 321 days.
Conclusions
Diagnosis and therapy of ILD‐LC is challenging and patients have a very limited survival. A significant proportion of patients could only receive palliative care indicating the need for better management strategies in this special patient population. The evaluation of the effect of cotreatment with antifibrotics needs further study.
Key points
• Interstitial lung diseases are often associated with lung cancer
• Diagnosis is challenging and therapy often limited due to underlying lung disease. Patients received platinum based chemotherapy or only supportive care.
Almonertinib was included in the first-line treatment of non-small cell lung cancer (NSCLC) with EGFR T790M mutations by the Chinese Society of Clinical Oncology (CSCO) in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid-liquid extraction with tert-butyl methyl ether, an XSelect HSS T3 column (2.1×100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib-D3 (internal standard, IS). The analytes were detected using an AB Sciex Triple Quad 5500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5-200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.
Objectives
To assess pathogen distributions and antimicrobial sensitivity characteristics in non-small cell lung cancer (NSCLC) patients diagnosed with severe radiation pneumonitis with secondary infections.
Methods
Data from 1746 NSCLC patients diagnosed with severe radiation pneumonitis following thoracic radiotherapy from January 2009 - December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in secondary lung infections patients were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and ROC curves.
Results
Overall, 44.5% (777/1746) NSCLC patients with severe radiation pneumonitis were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (206/899, 27%), Klebsiella pneumonia (200/899, 26.2%), and Pseudomonas aeruginosa (104/899, 13.6%) being most common. Carbapenems and cefoperazone-sulbactam resistance rates of 52.7%/32.2%, 28.8%/26.4%, and 23.7%/20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% severe radiation pneumonitis patients. Independent risk factors for infection-related death included poor performance status (PS) scores, inappropriate empirical antimicrobial treatment, bacteria/fungal co-infection, and lack of empirical antifungal treatment. ROC curves showed the cut-off value of empirical antifungal treatment duration was 9 (AUC=0.819).
Conclusion
For severe radiation pneumonitis patients with secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. While this represents a promising treatment approach for severe radiation pneumonitis patients with secondary lung infections prior to antibacterial susceptibility testing, further prospective validation is essential.
Immune checkpoint inhibitor (ICI) therapy is now in widespread clinical use for the treatment of lung cancer. Although patients with autoimmune disease and other comorbidities were excluded from initial clinical trials, emerging real-world experience suggests that these promising treatments may be administered safely to individuals with inactive low-risk autoimmune disease such as rheumatoid arthritis or psoriasis, mild to moderate renal and hepatic dysfunction, and certain chronic viral infections. Considerations for ICI in autoimmune disease populations include exacerbations of the underlying autoimmune disease, increased risk of ICI-induced immune-related adverse events, and potential for compromised efficacy if patients are receiving chronic immunosuppression. Immune checkpoint inhibitor use in higher-risk autoimmune conditions, such as myasthenia gravis or multiple sclerosis, requires careful evaluation on a case-by-case basis. Immune checkpoint inhibitor use in individuals with solid organ transplant carries a substantial risk of organ rejection. Ongoing research into the prediction of ICI efficacy and toxicity may help in patient selection, treatment, and monitoring.
