Risk factors of immune checkpoint inhibitor-related pneumonitis after neoadjuvant immunochemotherapy for resectable NSCLC.

BACKGROUND: The incidence of checkpoint inhibitor-associated pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) has been substantiated through large-scale clinical trials or real-world studies. However, reports on CIP incidence within the context of neoadjuvant immunotherapy for resectable NSCLC remain scarce. This study endeavors to investigate the incidence, risk factors, and outcomes of CIP in patients with resectable NSCLC receiving neoadjuvant immunochemotherapy. METHODS: A retrospective, case-control study was conducted on patients diagnosed with NSCLC stages IIA-IIIB who received neoadjuvant immunochemotherapy between January 2018 and September 2022. Patients were stratified into two groups based on the presence or absence of CIP, facilitating a comparative analysis of clinical characteristics, treatment modalities, physiological indicators, and prognostic outcomes . RESULTS: The study cohort comprised 245 patients, with 11.4% (28/245) experiencing CIP. The median period of CIP onset was 70 (range, 40-221) days. The incidence of severe CIP (grade 3-4) was 3.7% (9/245). Patients with CIP showed a higher all-cause mortality rate of 21.4% (6/28) compared to that of patients without CIP. Those who developed CIP exhibited elevated body mass index (BMI) values (p = 0.028) and increased fibrinogen (FIB) levels (p < 0.001), alongside a significant decrease in both diffusing capacity for carbon monoxide (DLCO)% pred (p = 0.001) and DLCO/VA% pred (p = 0.021) after neoadjuvant therapy compared to pre-indicators. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of three assessed variables (FIB levels, BMI, DLCO) reached 0.806 in predicting CIP occurrence at an early stage. CONCLUSIONS: This cohort demonstrated that elevated BMI, increased FIB levels, and decreased pulmonary diffusion function after neoadjuvant therapy are risk factors of CIP occurrence. Early assessment and continuous monitoring of these indicators are imperative for the predictive identification of CIP, enhancing patient management and outcomes.

Acute cardiac tamponade after Endostar treatment of non-small cell lung cancer: A case report.

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.

Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD. METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model. RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection. CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Risk Factors Analysis of AKI in Patients with Primary Non-small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitor.

INTRODUCTION: To investigate the risk factors of Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1(PD-L1) inhibitor associated acute kidney injury (AKI) in patients with primary non-small cell lung cancer (NSCLC) and construct a predictive model. METHODS: 120 NSCLC patients were selected as the research subjects and their clinical data were collected. Patients were divided into AKI and Non-AKI (N-AKI) group based on the development of AKI. Exploring the risk factors of PD-1P/D-L1 inhibitor related AKI in NSCLC patients using multivariate logistic regression analysis and visualized the logistic regression analysis to obtain a nomogram model. Meanwhile, evaluate the predictive value of the model. RESULTS: The results of multivariate analysis showed that the presence of extrarenal immune related adverse reactions (irAEs) is a risk factor for PD-1/PD-L1 inhibitor related AKI in NSCLC patients; At the same time, the risk of developing PD-1/PD-L1 inhibitor related AKI in NSCLC patients increases with increasing serum creatinine (SCr) and C-reactive protein (CRP) levels, decreasing baseline estimated glomerular filtration rate (eGFR) levels (P < .05). The analysis results of receiver operator characteristic curve (ROC), calibration curve, and decision curve show that the model has good discrimination and accuracy, and can achieve a high clinical benefit rate. CONCLUSION: Primary NSCLC patients with extrarenal irAEs, high levels of SCr and CRP, and low levels of eGFR have a higher risk of AKI after PD-1/PD-L1 inhibitor treatment. Establishing a predictive model with high accuracy is more conducive to early detection of high-risk patients. DOI: 10.52547/ijkd.7964.

QT-Interval Prolongation, Torsades de Pointes, and Heart Failure With EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: Systematic Review.

A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure (HF) in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR) TKIs. Of 296 identified publications, 95 met eligibility criteria and were abstracted for QTp/TdP and HF outcomes (QTp/TdP: 83 publications, including 5 case study publications; HF: 79 publications, including 6 case study publications [involving 8 patients]). QTp incidence ranged from 0% to 27.8% in observational studies and from 0% to 11% in clinical trials, with no deaths due to QTp. There were no TdP events or deaths due to TdP. The incidence of HF ranged from 0% to 8%, and HF mortality rates ranged from 0% to 4%. Patients receiving treatment with EGFR TKIs should be monitored for signs of QTp, TdP, and HF per prescribing information. Standardized definitions and methods to improve monitoring of QTp, TdP, and HF-related events are needed in patients with NSCLC.

Effective Differences between 2D and 3D Planned Brachytherapy in Lung Cancer: An Institutional Retrospective Study.

Background and Objectives: Advanced lung cancer is usually manifested by endoluminal tumor propagation, resulting in central airway obstruction. The objective of this study is to compare the high dose rate brachytherapy treatment outcomes in non-small-cell lung cancer (NSCLC) depending on the treatment planning pattern-two-dimension (2D) or three-dimension (3D) treatment planning. Materials and Methods: The study was retrospective and two groups of patients were compared in it (a group of 101 patients who underwent 2D planned high-dose-rate endobronchial brachytherapy (HDR-EBBT) in 2017/18 and a group of 83 patients who underwent 3D planned HDR-EBBT between January 2021 and June 2023). Results: In the group of 3D planned brachytherapy patients, there was a significant improvement in terms of loss of symptoms of bronchial obstruction (p = 0.038), but no improvement in terms of ECOG PS (European Cooperative Oncology Group Performance Status) of the patient (p = 0.847) and loss of lung atelectasis (if there was any at the beginning of the disease) (p = 0.781). Two-year overall survival and time-to-progression periods were similar for both groups of patients (p = 0.110 and 0.154). Fewer treatment complications were observed, and 91.4% were in 3D planned brachytherapy (BT) patients. Conclusions: Three-dimensionally planned HDR-EBBT is a suggestive, effective palliative method for the disobstruction of large airways caused by endobronchial lung tumor growth. Independent or more often combined with other types of specific oncological treatment, it certainly leads to the loss of symptoms caused by bronchial obstruction and the improvement of the quality of life of patients with advanced NSCLC. Complications of the procedure with 3D planning are less compared to 2D planned HDR-EBBT.

Longitudinal Study on Changes of Cancer-Related Fatigue in Elderly Patients with Postoperative Chemotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: Cancer-related fatigue (CRF) stands out as one of the most prevalent subjective adverse reactions experienced by patients following chemotherapy, often resulting in unfavorable symptoms for elderly non-small cell lung cancer (NSCLC) patients during chemotherapy. Hence, the aim of this study was to explore the fluctuations in CRF levels among elderly NSCLC patients undergoing chemotherapy. METHODS: This retrospective study involved 400 elderly patients diagnosed with NSCLC. Standardized guidelines were employed to direct patient care following lung cancer surgery (T0), subsequent to the first (T1), second (T2), third (T3), and fourth (T4) cycles of chemotherapy. At various intervals, all patients underwent assessments utilizing the Piper Fatigue Scale, Karnofsky Performance Status (KPS) Scale, Pittsburgh Sleep Quality Index (PSQI) Scale, and Connor-Davidson Resilience Scale. Additionally, serum levels of IL-6 and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Throughout the treatment regimen, patients exhibited a declining trend in CRF, CD-RISC, and KPS scores (p < 0.05, T0 vs T4), whereas the PSQI score demonstrated a notable increase (p < 0.05, T0 vs T4). Furthermore, ELISA results revealed that as treatment advanced, the average levels of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α during the T4 period significantly decreased compared to those at T0 (p < 0.05). CONCLUSION: As the number of chemotherapy treatments for elderly NSCLC patients increased, the severity of CRF and the manifestations of sleep disorders were escalated. Additionally, physical function, psychological resilience, as well as IL-6 and TNF-α levels, exhibited a downward trend.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia â ¡ (J-EPOCC â ¡)-Disease Awareness and Issues Related to Cancer Cachexia Among Healthcare Professionals].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC)was conducted among cancer patients, their families and healthcare professionals in Japan, and it showed that the term"cancer cachexia"was highly recognized among health care professionals, whereas the staging and criteria for cancer cachexia defined by European Palliative Care Research Collaborative( EPCRC)was less understood. Also, many healthcare professionals tended to consider the term"cancer cachexia" as the terminal stage of cancer, and most of them lacked the knowledge that cancer cachexia is a disease complication which is potentially developed from the early stage of cancer. Since anamorelin was approved in 2021 for"Cancer cachexia in unresectable advanced or recurrent of non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCC Ⅱ) was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their families and healthcare professionals1). The results for healthcare professionals showed that the awareness of the staging and criteria has increased among doctors in 2022 compared with 2019, and an increasing number of doctors considered"cancer cachexia"was associated with loss of muscle mass, totally body weight loss, appetite loss and systemic inflammation that may occur in early stages of cancer. On the other hand, awareness of staging and diagnostic criteria for cancer cachexia has not remarkably changed among medical staff since 2019, with levels of awareness varying among those with different job categories. Therefore, in order to achieve early detection and intervention of cancer cachexia, it is necessary to raise the awareness of cancer cachexia among not only doctors but also medical staff by increasing their opportunities to get to know the disease condition, diagnosis, and treatment of cancer cachexia.

Burden of comorbidities: Osteoporotic vertebral fracture during non-small cell lung cancer - the BONE study.

INTRODUCTION: Immunotherapy and targeted therapy have extended life expectancy in non-small cell lung cancer (NSCLC) patients, shifting it into a chronic condition with comorbidities, including osteoporosis. This study aims to evaluate the prevalence and incidence of osteoporotic vertebral fracture (OPVF) during NSCLC follow-up, identify risk factors of OPVF, and determine the impact on overall survival (OS). METHODS: We performed a longitudinal single-center retrospective cohort study involving patients with histologically proven NSCLC of any stage. Chest-abdomen-pelvis computed tomography (CAP CT) at diagnosis and during follow-up were double-blind reviewed to determine OPVF site, count, type, time to incident OPVF, and trabecular volumetric bone density (TVBD). An institutional expert committee adjudicated discrepancies. Binary logistic regression was used to predict the occurrence of incident OPVF. OS was calculated using the Kaplan-Meier method. RESULTS: We included 289 patients with a median follow-up of 29.7 months. OPVF prevalence was 10.7% at inclusion and 23.2% at the end of follow-up. Cumulative incidence was 12.5%, with an incidence rate of 4 per 100 patient-years. Median time to incident OPVF was 13 months (IQR: 6.7-21.2). Seven of the 36 patients with incident OPVF received denosumab or bisphosphonates. In multivariable analysis, independent risk factors for incident OPVF were BMI < 19 kg/m2 (OR: 5.62, 95%CI 1.84-17.20, p = 0.002), lower TVBD (OR: 0.982 per HU, 95%CI 0.97-0.99, p = 0.001) and corticosteroid use (OR: 4.77, 95%CI: 1.76-12.89, p = 0.001). OPVF was not significantly associated with OS. CONCLUSIONS: Osteoporosis should be screened for in NSCLC patients. Thoracic oncologists must broaden the use of steroid-induced osteoporosis recommendations.

Efficacy and safety of local ablative therapy for patients with NSCLC and coexisting interstitial lung disease.

BACKGROUND: The effective therapeutic approach is still an unmet need for patients diagnosed with both lung cancer and interstitial lung disease (ILD). This is primarily due to the possible risk of ILD exacerbation caused by surgery or radiotherapy. The current study aimed to investigate the efficacy and safety of local ablative therapy (LAT) for this specific population. METHODS: Consecutive patients with non-small cell lung cancer (NSCLC) and ILD who received LAT between January 2018 and August 2022 were enrolled, and propensity score matching (PSM) was utilized to match the non-ILD group. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), adverse events (AEs) and hospital length of stay (HLOS). RESULTS: The PSM algorithm yielded matched pairs in the ILD group (n = 25) and non-ILD group (n = 72) at a ratio of 1:3. There were no statistically significant differences in RFS (median 16.4 vs. 18 months; HR = 1.452, p = 0.259) and OS (median: not reached vs. 47.9 months; HR = 1.096, p = 0.884) between the two groups. Meanwhile, no acute exacerbation of ILD was observed in the ILD group. However, the incidence of pneumothorax, especially pneumothorax requiring chest tube drainage, was significantly higher (36.0% vs. 11.2%, p = 0.005) among patients with NSCLC and co-existing ILD, which resulted in longer HLOS (p = 0.045). CONCLUSION: Although ILD was associated with a higher incidence of pneumothorax, the efficacy of LAT for NSCLC patients with ILD was comparable to those without ILD, suggesting that LAT might be a reliable and effective treatment option for this population, particularly in the early stage.

The prognostic significance of lymph nodes in patients with pT1c33N0M0 non-small cell lung cancer: a retrospective study.

Objective: The objective of this study was to appraise the prognostic impact of lymph nodes in patients diagnosed with pT1c33N0M0 non-small cell lung cancer (NSCLC) and to delve into the prognostic significance of lymph nodes located at the N1 lymph node station in this patient cohort. Methods: A retrospective analysis of clinical data was conducted for 255 patients diagnosed with pT1c33N0M0 NSCLC. Lymph nodes were tabulated and categorized into three groups (0-10 nodes, 11-16 nodes, >16 nodes). Clinical data among these three groups of pT1c33N0M0 NSCLC patients were compared. We conducted both univariate and multivariate analyses to pinpoint the factors that impact the prognosis of patients with pT1c33N0M0 non-small cell lung cancer (NSCLC). Additionally, we employed receiver operating characteristic (ROC) curve analysis to pinpoint the optimal lymph node criteria at the N1 station for prognostic prediction in pT1c33N0M0 NSCLC patients. Results: Within the cohort of 255 individuals afflicted with pT1c33N0M0 non-small cell lung cancer (NSCLC), a comprehensive tally of 3,902 lymph nodes was diligently established, yielding an average of 15.3 nodes for each patient. Multivariate analysis demonstrated that tumor size, T stage, and lymph nodes were independent factors significantly impacting the prognosis of pT1c33N0M0 NSCLC patients (P < 0.05). ROC curve analysis revealed an area under the curve of 0.6982 for predicting prognosis using N1 station in pT1c33N0M0 NSCLC patients. The maximum Youden index was observed at an N1 station of 2.7 nodes. Patients with N1 station ≥ three nodes had significantly better prognoses compared to those with < 3 nodes (both P < 0.05). Conclusion: Lymph nodes serve as an independent prognostic factor for pT1c33N0M0 NSCLC patients. Detecting at least three or more lymph nodes at the N1 station is associated with a more favourable prognosis in pT1c33N0M0 NSCLC patients.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial.

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Main outcomes and measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.