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Background: Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. Methods: In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. Results: GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. Conclusions: Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income. [ABSTRACT FROM AUTHOR]

Background: For patients with lung cancer, timely identification of new lung lesions as infectious or noninfectious, and accurate identification of pathogens is very important in improving OS of patients. As a new auxiliary examination, metagenomic next-generation sequencing (mNGS) is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases, compared with conventional microbial tests (CMTs). We designed this study to find out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavage fluid (BALF). Materials and Methods: This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage (BAL) and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Affiliated Hospital of Sun Yat-sen University. 164 patients were included in this study. Patients were categorized into the pulmonary non-infectious disease (PNID) group (n = 64) and the pulmonary infectious disease (PID) group (n = 100) groups based on final diagnoses. Results: BALF mNGS increased the sensitivity rate by 60% compared to CMTs (81% vs. 21%, p < 0.05), whereas there was no significant difference in specificity (75% vs. 98.4%, p > 0.1). Among the patients with PID, bacteria were the most common cause of infection. Fungal infections occurred in 32% of patients, and Pneumocystis Yersini was most common. Patients with Tyrosine kinase inhibitors (TKIs) therapy possess longer overall survival (OS) than other anti-cancer agents, the difference between TKIs and immuno-checkpoint inhibitors (ICIs) was insignificant (median OS TKIs vs. ICIs vs. Anti-angiogenic vs. Chemo vs. Radiotherapy = 76 vs. 84 vs. 61 vs. 58 vs. 60). Conclusions: our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection, and was outstanding in identifying Pneumocystis infection. It could be able to help physicians adjust the follow-up treatment to avoid the abuse of antibiotics. [ABSTRACT FROM AUTHOR]

Objective • This study investigated the expression and clinical significance of Melanoma Associated Antigen (MAGE)-A proteins and mRNA in patients with nonsmall cell lung cancer (NSCLC). Methods • A retrospective study was conducted, and we selected a cohort of 88 NSCLC patients treated at our hospital from January 2015 to January 2020. Adjacent tissues were chosen as controls. The expression of MAGE-A proteins in lung cancer and adjacent tissues was assessed via Western blot, while MAGE-As mRNA expression was measured using RT-PCR. Results • The relative expression levels of MAGE-A proteins and mRNA in NSCLC tissues were significantly higher than those in adjacent tissues (P < .05), with values of (0.343 ± 0.101) and (0.728 ± 0.112), respectively. Furthermore, MAGE-As protein expression was significantly higher in stage III - IV lung cancer compared to stage I - II (P < .05). No significant differences were observed in MAGE-A protein expression concerning gender, age, tumor diameter, pathological type, and differentiation degree (P > .05). The relative expression of MAGE-As mRNA was significantly higher in clinical stage III - IV and moderately differentiated lung cancer tissues compared to stage I - II and well-differentiated tissues (P < .05). No significant differences were found in MAGE-As mRNA expression concerning gender, age, tumor diameter, and pathological type (P > .05). Patients with high MAGE-As mRNA expression had a significantly shorter median overall survival of 33 months (95% CI: 31.64-34.36) compared to those with low MAGE-As mRNA expression (P < .05). However, no significant difference was observed in median overall survival between patients with high and low MAGE-As protein expression (P > .05). Conclusions • In NSCLC, the up-regulation of MAGE-A proteins and mRNA is associated with clinical stage and differentiation degree, warranting further investigation. [ABSTRACT FROM AUTHOR]

Objective • Lung cancer patients mostly had different degrees of impaired pulmonary function, and these damage also significantly affect quality of life. The concept of pulmonary rehabilitation applicable to patients with chronic respiratory diseases is also applicable to patients with lung cancer. The current application of pulmonary rehabilitation for lung cancer is inconsistent, and reliable guidelines are lacking. The purpose of this study was to investigate the effect of pulmonary rehabilitation exercise based on wearable device pedometer on lung cancer patients with impaired pulmonary function, and to find a suitable pulmonary rehabilitation program for patients with lung cancer. Methods • In this retrospective study, 100 lung cancer patients with impaired pulmonary function were included. Among them, 51 patients received pulmonary rehabilitation exercise based on a wearable device pedometer (Experiemental group), while 49 received routine nursing mode (Control group). The respiratory function, quality of life, and sports endurance of the two groups were observed. Results • The incidence of postoperative atelectasis, pulmonary infection, hypoxemia, postoperative oxygen therapy time, chest tube indwelling time, and postoperative hospital stay in the experimental group were significantly lower than those in the control group (P < .05); The FEV1, FVC and FVE1% of the experimental group were significantly higher than those of the control group after intervention (all P < .05). Conclusion • Pulmonary rehabilitation exercise based on a wearable device pedometer can effectively improve the respiratory function and exercise endurance of lung cancer patients with impaired pulmonary function and can improve the quality of life and reduce the length of hospital stay. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the impact of mind–body exercise (yoga, tai chi, qigong, etc.) on lung cancer. Methods: We performed a literature search of the electronic databases PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, WanFang Data, and VIP from their inception to 16 May 2023. The primary outcome was the 6-min walk test (6MWT), while the secondary outcomes were anxiety levels and quality of life (QoL). Two independent reviewers performed the data extraction using a predefined protocol and assessed the risk of bias using the Cochrane risk of bias (ROB) tool for randomized controlled trials, with differences agreed by consensus. Meta-analysis was performed using RevMan 5.4 and Stata 15 software to analyze the extracted data. Results: This meta-analysis included a total of 11 studies involving 897 patients. The results indicated that compared to the usual care group, lung cancer patients in the mind–body exercise group could increase the 6-min walk distance (5 studies, 346 participants, WMD: 18.83, 95% CI (7.55, 30.10) P = 0.001), reduce anxiety levels (4 studies, 362 participants, SMD: − 1.51, 95% CI (− 1.74, − 1.27), P < 0.05), and enhance the overall quality of life (6 studies, 594 participants, SMD: 0.71, 95% CI (0.10, 1.31), P = 0.02). The overall certainty of the evidence for all outcomes was low; seven studies were judged to be at low risk of bias, and four studies were judged to be at moderate risk of bias. Conclusion: Mind–body exercise could improve exercise capacity in lung cancer survivors, reduce anxiety, and positively affect overall quality of life. PROSPERO registration number: CRD42023426800 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the impact of mind–body exercise (yoga, tai chi, qigong, etc.) on lung cancer. Methods: We performed a literature search of the electronic databases PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, WanFang Data, and VIP from their inception to 16 May 2023. The primary outcome was the 6-min walk test (6MWT), while the secondary outcomes were anxiety levels and quality of life (QoL). Two independent reviewers performed the data extraction using a predefined protocol and assessed the risk of bias using the Cochrane risk of bias (ROB) tool for randomized controlled trials, with differences agreed by consensus. Meta-analysis was performed using RevMan 5.4 and Stata 15 software to analyze the extracted data. Results: This meta-analysis included a total of 11 studies involving 897 patients. The results indicated that compared to the usual care group, lung cancer patients in the mind–body exercise group could increase the 6-min walk distance (5 studies, 346 participants, WMD: 18.83, 95% CI (7.55, 30.10) P = 0.001), reduce anxiety levels (4 studies, 362 participants, SMD: − 1.51, 95% CI (− 1.74, − 1.27), P < 0.05), and enhance the overall quality of life (6 studies, 594 participants, SMD: 0.71, 95% CI (0.10, 1.31), P = 0.02). The overall certainty of the evidence for all outcomes was low; seven studies were judged to be at low risk of bias, and four studies were judged to be at moderate risk of bias. Conclusion: Mind–body exercise could improve exercise capacity in lung cancer survivors, reduce anxiety, and positively affect overall quality of life. PROSPERO registration number: CRD42023426800 [ABSTRACT FROM AUTHOR]

Background: Lung cancer continues to be the leading cause of cancer‑related deaths in men and women. A breakdown by level of economic development shows no differences in cancer deaths in men but a higher rate of lung cancer deaths in women in industrialized countries as compared with developing nations. The risk factors for lung cancer most commonly include lifestyle, environmental, and occupational exposures. The role these factors play varies depending on geographic location, sex and race characteristics, genetic predisposition, as well as their synergistic interactions. Materials and Methods: It was a hospital‑based registry, wherein hospitals were selected from three zones-north, central, and south zones of Kerala. The study was registered with clinical trial registry of India with Registration No. CTRI/2021/02/031299. Registry of lung cancer patients was prepared at all sites and institutional ethical clearance was received from all sites. All patients with primary lung cancer, histologically proven of all age groups were included in the study. Results: A total of 761 patients were registered from six teaching hospitals in Kerala who were diagnosed with primary lung cancer during the period 2017–2019. The mean age of the study population was 65.1 ± 10.2 years. Of all, 81.1% of them were males and 18.9% were females. Histologically, 56.4% had adenocarcinoma and 25.6% had squamous cell carcinoma. Conclusion: It was observed that the proportion of females diagnosed with primary lung cancer is increasing. Patients get diagnosed at a later stage of the disease, which calls for screening and early detection of lung cancer. As it accounts for the highest mortality among all other cancers, there is high scope for prevention and screening strategies. [ABSTRACT FROM AUTHOR]

Background: Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results: Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions: We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. [ABSTRACT FROM AUTHOR]

The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer. [ABSTRACT FROM AUTHOR]

Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) is a common type of lung cancer with high incidence and mortality rate. Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. This study aimed to reveal TMB involved in the mechanisms of LUSC and develop a model to predict the overall survival of LUSC patients. The information of patients with LUSC were obtained from the cancer genome atlas database (TCGA). Differentially expressed genes (DEGs) between low- and the high-TMB groups were identified and taken as nodes for the protein–protein interaction (PPI) network construction. Gene oncology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were used to investigate the potential molecular mechanism. Then, we identified the factors affecting the prognosis of LUSC through cox analysis, and developed a risk score signature. Kaplan–Meier method was conducted to analyze the difference in survival between the high- and low-risk groups. We constructed a nomogram based on the risk score model and clinical characteristics to predict the overall survival of patients with LUSC. Finally, the signature and nomogram were further validated by using the gene expression data downloaded from the Gene Expression Omnibus (GEO) database. 30 DEGs between high- and low-TMB groups were identified. PPI analysis identified CD22, TLR10, PIGR and SELE as the hub genes. Cox analysis indicated that FAM107A, IGLL1, SELE and T stage were independent prognostic factors of LUSC. Low-risk scores group lived longer than that of patients with high-risk scores in LUSC. Finally, we built a nomogram that integrated the clinical characteristics (TMN stage, age, gender) with the three-gene signature to predict the survival probability of LUSC patients. Further verification in the GEO dataset. TMB might contribute to the pathogenesis of LUSC. TMB-associated genes can be used to develope a model to predict the OS of lung squamous cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Nailfold capillary abnormalities are typically observed in patients with systemic sclerosis and are also often found in patients with polymyositis (PM) and dermatomyositis (DM). Nailfold capillary abnormalities in some patients with PM/DM were found to improve with immunosuppressant treatment. However, the short-term changes in nailfold capillaries and their associations with disease activity have not been established yet. Additionally, there have been no reports on whether nailfold capillary abnormalities can change during the progression of malignant tumours. A man in his 60s with anti-transcriptional intermediate factor 1γ (anti-TIF-1γ) antibody-positive DM complicated with small cell lung carcinoma was treated with prednisolone (PSL) 70 mg, carboplatin (CBDCA) and etoposide (VP-16). His nailfold capillary abnormalities improved rapidly, and the tumour size decreased with treatment. Although chemotherapy was continued, abnormalities in the nailfold capillaries gradually recurred. The worsening of the capillary abnormalities prompted us to examine computed tomography scans, which showed the recurrence of lung cancer. After switching to second-line chemotherapy, the change in the nailfold capillary abnormalities was again in a parallel course with the disease status of lung cancer. Changes in nailfold capillaries may be useful not only for the diagnosis but also for the evaluation of the recurrence of malignant tumours with DM. [ABSTRACT FROM AUTHOR]

Background: Reversal of neuromuscular blockade (NMB) at the end of surgery is important for reducing postoperative residual NMB; this is associated with an increased risk of postoperative pulmonary complications (PPCs). Moreover, PPCs are associated with poor prognosis after video-assisted thoracoscopic surgery (VATS) for lobectomy. We compared the effects of two reversal agents, sugammadex and neostigmine, on the incidence of PPCs and duration of hospital stay in patients undergoing VATS lobectomy. Methods: After VATS lobectomy was completed under neuromuscular monitoring, the sugammadex group (n = 46) received sugammadex 2 mg/kg, while the neostigmine group (n = 47) received neostigmine 0.05 mg/kg with atropine 0.02 mg/kg after at least the third twitch in response to the train of four stimulation. The primary outcome was incidence of PPCs. The secondary outcomes were duration of hospital stay and intensive care unit (ICU) admission. Results: There was no significant difference in the incidence of PPCs for both the sugammadex and neostigmine groups (32.6% and 40.4%, respectively; risk difference = 0.08; 95% confidence interval = [−0.12, 0.27]; P = 0.434). The lengths of hospital (P = 0.431) and ICU (P = 0.964) stays were not significantly different between the two groups. Conclusions: The clinical use of sugammadex and neostigmine in NMB reversal for patients undergoing VATS lobectomy was not significantly different in the incidence of PPCs and duration of hospital and ICU stay. [ABSTRACT FROM AUTHOR]

Lung cancer is the most commonly occurring cancer in men and the third most commonly occurring cancer in women. Contrary to other cancers, lung cancer often occurs in patients with comorbidities that can prevent the realisation of some treatments. The recommended treatment for patients presenting with stage I non-small cell lung cancer (NSCLC) is an anatomical surgical resection-lobectomy- and a systematic lymph node dissection. Many patients are, however, unfit to undergo surgery and consequently they often do not receive any curative therapy. This involves the elderly patients or patients with many co-morbidities. When an elderly patient with co-morbidities comes to the thoracic surgeon with early-stage lung cancer, if he is healthy and in good general condition he is taken to the operating room and undergoes lobectomy and lymph node dissection. If he is vulnerable and appropriate treatment is considered high risk he is treated with alternative therapies. SBRT is important alternative therapy. Stereotactic body radiation therapy (SBRT), interchangeably known as stereotactic ablative radiotherapy (SABR) is a modality that delivers ablative doses of radiation to extra-cranial targets with a degree of precision and accuracy above what can be reasonably achieved with conventionally fractionated external beam radiotherapy. Additionally, SBRT as a noninvasive therapy offers an attractive option for patients who are opposed to a surgical option. But questions have arisen regarding the suitability of SBRT for medically operable patients. Data from new trials are needed more than ever to inform and guide our multidisciplinary decisions for patients with earlystage NSCLC who are fit enough to undergo lung cancer surgery but may instead be more interestedin SBRT. In any case, good cooperation between surgeons and radiotherapists is of particular importance for the better treatment of these vulnerable patients. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is one of the most common types of cancer disease worldwide. Studies in the field show that the appearance of a pathology of this form causes changes not only in the patient's life, namely psychological problems, functional limitations and poorer health due to the clinical consequences of treatments, but also in their family, where caregivers often face the challenge of providing long-term daily care that induces a physical, psychosocial and financial burden (Borges et al., 2017; Hewitt et al., 2003; Tan et al., 2018). The main objective of the present study is to compare and relate the two groups (patients and caregivers) considering the quality of life (QoL) and symptoms of psychological distress (anxiety and depression). The total sample consisted of 30 patient/caregiver dyads. The instruments used were: Hospital Anxiety and Depression Scale; European Organization for Research and Treatment of Quality of Life Questionnaire (EORTC QLQ C-30) and its specific module for lung cancer (LC13); Caregiver Oncology Quality of Life Questionnaire (CarGOQoL) and Zarit Burden Interview Scale (ZBI). The results suggest the influence of depressive symptomatology on patients' QoL [F(1)=6.390; p<0.05] and depressive and anxious symptomatology and burden on caregivers' QoL [F(3)=7.815; p<0.001]. A positive association was found between depressive symptomatology of patients and caregivers (r=0.458; p=0.011) and differences in anxious symptomatology were also observed, with a higher result in the patient's group. [ABSTRACT FROM AUTHOR]

Hand-crafted radiomics has been used for developing models in order to predict time-to-event clinical outcomes in patients with lung cancer. Hand-crafted features, however, are pre-defined and extracted without taking the desired target into account. Furthermore, accurate segmentation of the tumor is required for development of a reliable predictive model, which may be objective and a time-consuming task. To address these drawbacks, we propose a deep learning-based radiomics model for the time-to-event outcome prediction, referred to as DRTOP that takes raw images as inputs, and calculates the image-based risk of death or recurrence, for each patient. Our experiments on an in-house dataset of 132 lung cancer patients show that the obtained image-based risks are significant predictors of the time-to-event outcomes. Computed Tomography (CT)-based features are predictors of the overall survival (OS), with the hazard ratio (HR) of 1.35, distant control (DC), with HR of 1.06, and local control (LC), with HR of 2.66. The Positron Emission Tomography (PET)-based features are predictors of OS and recurrence free survival (RFS), with hazard ratios of 1.67 and 1.18, respectively. The concordance indices of 68 % , 63 % , and 64 % for predicting the OS, DC, and RFS show that the deep learning-based radiomics model is as accurate or better in predicting predefined clinical outcomes compared to hand-crafted radiomics, with concordance indices of 51 % , 64 % , and 47 % , for predicting the OS, DC, and RFS, respectively. Deep learning-based radiomics has the potential to offer complimentary predictive information in the personalized management of lung cancer patients. [ABSTRACT FROM AUTHOR]

With the increasing incidence rate of lung cancer patients, early diagnosis could help in reducing the mortality rate. However, accurate recognition of cancerous lesions is immensely challenging owing to factors such as low contrast variation, heterogeneity and visual similarity between benign and malignant nodules. Deep learning techniques have been very effective in performing natural image segmentation with robustness to previously unseen situations, reasonable scale invariance and the ability to detect even minute differences. However, they usually fail to learn domain‐specific features due to the limited amount of available data and domain agnostic nature of these techniques. This work presents an ensemble framework Deep3DSCan for lung cancer segmentation and classification. The deep 3D segmentation network generates the 3D volume of interest from computed tomography scans of patients. The deep features and handcrafted descriptors are extracted using a fine‐tuned residual network and morphological techniques, respectively. Finally, the fused features are used for cancer classification. The experiments were conducted on the publicly available LUNA16 dataset. For the segmentation, the authors achieved an accuracy of 0.927, significant improvement over the template matching technique, which had achieved an accuracy of 0.927. For the detection, previous state‐of‐the‐art is 0.866, while ours is 0.883. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate if laser-assisted resection is appropriate for large and/or central lung metastases, when stapler wedge resection is not feasible, to determine whether this technique can be an alternative to lobectomy. All patients who underwent laser-assisted resection for large and/or central metastases were selected for the study. For comparison, patients who underwent lobectomy for metastases between 2005 and 2017 were reviewed. All resections were performed with a 1318-nm Nd:YAG laser. Perioperative features and long-term oncological outcomes were investigated. Some aspects and drawbacks of laser resection were also investigated. Among 89 patients, 42 (47%) underwent laser resection and 47 underwent lobectomy. Complete resection was achieved in 91% of laser resections and in 98% of lobectomies. The operative time, postoperative drainage time, and length of stay were significantly shorter in patients who underwent laser resection than in those who underwent lobectomy. Severe postoperative complications tended to be more frequent after lobectomy. The 5-year survival was 66% and 54% after laser resection and lobectomy respectively; the 5-year disease-free survival was 35% and 32% after laser resection and lobectomy respectively. No differences were found in long-term outcomes between the two techniques. Our experience showed that laser resection, when performed for large/central metastases, resulted in comparable survival and obtained better perioperative outcomes with respect to lobectomy. We believe that laser resection can be proposed as a reliable and advantageous lung-sparing technique, as an alternative to lobectomy for metastasectomy, when stapler wedge resection is not feasible. [ABSTRACT FROM AUTHOR]

Purpose: The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naïve lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI).Methods: Treatment-naïve lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate.Results: Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p < 0.0001). Higher proportion of patients with moderate-severe pain took opioids compared with those with mild pain (52% vs. 16%, p < 0.0001). Patients on opioids also reported significantly worse scores for five other cancer-specific core symptoms and all six symptoms rating interference with daily life. Only 15% of patients with higher composite score for depression-related symptoms were on antidepressants. However, patients taking antidepressants did not significantly differ in any individual MDASI symptom scores compared with those not on antidepressants (p = 0.4858).Conclusions: Our results suggest a need for better screening for pain and depression and optimization of pain management in treatment-naïve lung cancer patients since their poor functional status may result in suboptimal cancer therapy. [ABSTRACT FROM AUTHOR]

Self-expandable metallic stents (SEMSs) have been widely used in the treatment of malignant central airway obstruction. However, few reports focus on the treatment of atelectasis and how to estimate the prior probability of success via SEMSs placement, This current study aimed to study the safety and effectiveness of SEMSs for the treatment of obstructive atelectasis, and the value of preoperative CT enhancement for ventilation of atelectasis via SEMSs placement. A total of 35 patients with obstructive atelectasis (29 male and 6 female) was included from February 2012 to March 2018. The procedures were performed under fluoroscopic guidance, and bronchoscopic laser resection was performed for severe restenosis cases after SEMSs placement. Clinical and functional pulmonary data were recorded before and 3 months after the procedure. Follow-up involved clinical data and radiographic techniques at 48 h and at 1-, 3-, 6-, and 12-month intervals. Thirty-eight SEMSs were successfully implanted in 34 patients, included 29 Y type tracheal stents, 4 small y stents, and 5 straight airway stents. After stenting, 26 cases showed full ventilation, and 3 cases were partially ventilated. The technical success and clinical success was 97.1% and 82.9%, respectively. A higher maximum enhancement CT value was found in patients with full ventilation. Mean follow-up time was 18.8 ± 4.0 months. Eight cases showed restenosis and received endoscopic laser resection, included 1 case underwent removal and 3 cases received second stenting. There were 2 cases of perioperative non-operative death, and 11 cases of post-discharge death (2 cardiac deaths and 9 malignant tumors). The survival rates of 3 months, 1 year and 2 years were 78.6%, 58.5% and 58.5%, respectively. In conclusion, SEMSs placement is safe and effective for obstructive atelectasis, and the preoperative CT enhancement played an important role in estimating the prior probability of success in the treatment of atelectasis via SEMSs placement. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate overall survival in patients with lung cancer with brain metastasis. Our other aim was to investigate prognostic value of the maximum standardized uptake value (SUVmax) of primary tumor on 18Fluorine-fluorodeoxyglucose positron emission tomography / computed tomography (18F-FDG PET / CT) FDG PET / CT and other clinicopathological parameters. Material and Methods: Fifty-eight patients with lung cancer who underwent for oncologic purpose and had metastatic lesions in the brain were included in the study. The location of the primary lung mass and whether other organ metastases presence was evaluated on the 18F-FDG PET / CT. In axial images, the volume of interest (VOI) was plotted semi-automatically to include lung tumor tissue and SUVmax of the primary lung tumor was measured. Survival analyzes were performed with Kaplan-Meier survival analysis. The prognostic value of the parameters was evaluated using Cox regression analysis. Results: Of the 58 patients included in the study, 6 (10%) were female and 52 (90%) were male. The mean age was 64.8 ± 9.5 years. The mean SUVmax of primary tumor was 10.4 ± 4.5. Median survival was 7 months. Patient age and localization of the primary tumor were prognostic factors for survival in univariate analysis, whereas sex, SUVmax of primary tumor, presence of distant metastasis outside the brain, histologic subtype, surgical status of the metastatic brain mass and treatment type were not. Overall survival was lower in patients with primary tumor located in the left lung than in the right lung. Conclusion: In conclusion, age and localization of primary tumor are prognostic factors, whereas SUVmax of primary tumor does not appear to be a prognostic factor in lung cancer patients with brain metastases. [ABSTRACT FROM AUTHOR]

Objective Lung cancer is the leading cause of cancer related deaths among women and men worldwide. The most important determinant of survival is the TNM staging system and the most effective treatment is surgery. In this study we aimed to investigate the local and distant recurrence effects of tumor pathologic features in patients with non- small cell lung cancer (NSCLC) who underwent complete resection. Material and Methods 57 patients who underwent complete resection of NSCLC in our clinic were evaluated retrospectively between 2008 and 2012. Histological type, differantiation, presence of necrosis, visceral-parietal pleural involvement, N1-N2 involvement, pathological stage, local and distant recurrence, development, distant recurrence location and their effects on 3- year survival were compared. Results Tumor histopathologic features and local and distant recurrence were not statistically significant. Among the parameters affecting 3-year survival, differantiation, pathological stage, parietal pleural involvement, distant recurrence development, distant recurrence location and postoperative distant recurrence time were statistically significant. Conclusion The tumor pathological features of NSCLC patients do not seem to be an effective parameter for local and distant recurrence. [ABSTRACT FROM AUTHOR]

A growing interest concerns arterial thromboembolic disease in cancer patients. As platelets may be key players in this process, investigation of platelet aggregation in cancer patients is of importance. We aimed to investigate platelet aggregation in patients with lung cancer prior to surgery and during video-assisted thoracoscopic surgery (VATS) lobectomy compared with lobectomy performed through a thoracotomy. We included 93 patients (VATS + low molecular weight heparin (LMWH), n = 32; VATS no LMWH, n = 31; thoracotomy + LMWH, n = 30). Data obtained from 121 healthy individuals were used for comparison prior to surgery. Platelet aggregation was analysed by impedance aggregometry using adenosine diphosphate 6.5 μM (ADPtest) and collagen 3.2 μg/mL (COLtest) as agonists. Prior to surgery, platelet aggregation was significantly increased in both VATS-patients (ADPtest, p < .0001; COLtest, p = .0002) and patients undergoing thoracotomy (ADPtest, p < .0001; COLtest, p < .0001) compared with healthy individuals. Platelet aggregation did not differ between VATS-patients and thoracotomy patients prior to surgery (p-values >.11). At the first postoperative day, VATS-patients demonstrated significantly higher collagen-induced platelet aggregation than preoperatively (p = .001), but the increase in platelet aggregation did not differ significantly between VATS and thoracotomy patients (p-values ≥.24). At the second postoperative day, platelet aggregation was significantly reduced in thoracotomy patients compared with the preoperative level (ADPtest, p = .002; COLtest, p = .05). In conclusion, platelet aggregation was significantly increased in patients with primary lung cancer prior to surgery compared with healthy individuals. At the first postoperative day, platelet aggregation was significantly higher than the preoperative level in VATS-patients; however, this increase did not differ between patient groups. [ABSTRACT FROM AUTHOR]

Introduction: Epidemiologic and preclinical data support the cancer prevention potential of rodent tuber (Tybonium Flagelliforme). We compared the overall outcome of patients who received a capsule extract of rodent tuber (CeRT) and refused chemotherapy or taking antineoplastic therapy on lung carcinoma. Method: We randomly assigned patients with lung carcinoma stage lll-IV who refused chemotherapy to receive CeRT 3.0 g a day for 90 days, evaluating symptoms (breathless, vomiting, nausea, chest pain, cough, and anorexia) during therapy while tumour mass in baseline and after treatment using thorax multislice computed tomography (MSCT) and analyzed base on the response evaluation criteria in solid tumors criteria (RECIST). Result: In the CeRT patient (n= 10) showed a significant reduction in complication symptoms, i.e., breathless, coughing, and chest pain than in the chemotherapy population (n= 10) significant reduction in 2 parameters (breathless and chest pain). On the thorax MSCT parameter, the CeRT showed a few reduction of tomour mass after treatment, while the chemotherapy illustrated a significant reduction of tumour mass after treatment. Value: The analysed clinical trials by giving CeRT provided evidence to increase the quality of life of lung cancer patients. Although CeRT is not as good as effect with chemotherapy effect in reducing the tomour mass, CeRT can reduce the symptom and highly valued by cancer patients. [ABSTRACT FROM AUTHOR]

Despite the importance of empathic communication in cancer patient outcomes, the majority of opportunities to respond empathically to a patient's concern within clinical consultations are "missed" (i.e., 70-90%), or not responded to by physicians. The present study examined the empathic opportunities and responses within clinical consultations of lung cancer patients and how these each are associated with patient-reported outcomes. Results indicate that lung cancer patients (n = 56) most commonly presented empathic opportunities related to emotions, anxiety was significantly associated with empathic opportunity type (p = .011), and physicians are most likely to respond with high empathy to statements around a patient making progress rather than bringing up a challenge or an emotion they felt (p = .031). The present study results highlight the need to train lung cancer physicians to respond with higher empathy to opportunities to respond to negative emotions, including mentions of challenges faced or emotions experienced, as these patients are at the highest risk of experiencing distress and the least likely to receive a high empathic response from physicians. [ABSTRACT FROM AUTHOR]

Accurate tracking of organ motion during treatment is needed to improve the efficacy of radiation therapy. This work investigates the feasibility of tracking an uncontoured target using the motion detected within a moving treatment aperture. Tracking was achieved with a weighted optical flow algorithm, and three different techniques for updating the reference image were evaluated. The accuracy and susceptibility of each approach to the accumulation of position errors were verified using a 3D-printed tumor (mounted on an actuator) and a virtual treatment aperture. Tumor motion up to 15.8 mm (peak-to-peak) taken from the breathing patterns of seven lung cancer patients was acquired using an amorphous silicon portal imager at ~ 7.5 frames/s. The first approach (INI) used the initial image detected, as a fixed reference, to determine the target motion for each new incoming image, and performed the best with the smallest errors. This method was also the most robust against the accumulation of position errors. Mean absolute errors of 0.16, 0.32, and 0.38 mm were obtained for the three methods, respectively. Although the errors are comparable to other tracking methods, the proposed method does not require prior knowledge of the tumor shape and does not need a tumor template or contour for tracking. Graphical abstract. [ABSTRACT FROM AUTHOR]

Introduction: An important part of the therapeutic process of patients with lung cancer undergoing palliative chemotherapy is to assess their mental well-being. Evaluation of the sense of coherence and acceptance of the disease, which reflects the degree of adaptation of the patient to live with the disease, provides information on this topic. Objective: The primary objective was to assess the level of sense of coherence and acceptance of the disease in patients with lung cancer during palliative chemotherapy as well as coherence and acceptance together with socio-demographic factors. The secondary objective was to assess the economic impact of lung cancer on these patients. Material and methods: The study involved 100 patients with lung cancer during palliative chemotherapy. The study was conducted using the Sense of Coherence Questionnaire (SOC-29), the Acceptance of Illness Scale, and a socio-demographic questionnaire. Results: The study group consisted mainly of men (66%), people with primary/vocational education (63%) and patients living in cities (59%). The average age of respondents was 62.8 years. 45% of patients had a high level of sense of coherence, and 44% had an average level. The average overall score of SOC was 143.9 points inside the upper range of average results. Levels of a sense of comprehensibility, manageability, and meaningfulness remained in close relation to the average level: 48.91, 51.33, and 43.66 points, respectively. The average acceptance of the disease was 45% with the average total of 27.21 points. Conclusions: Most patients during palliative chemotherapy because of lung cancer had average or high level of coherence and acceptance of the disease. The level of sense of coherence and acceptance of the disease was not affected by gender, age, education, or place of residence. Almost all patients incur costs associated with treatment, and in some of them the disease affected the source of income. [ABSTRACT FROM AUTHOR]

While the prognosis of metastatic non-small-cell lung cancer has shown significant progress these last years, notably with the discovery of oncogen-driven subtypes and the development of targeted therapies, significant improvements are still needed. More recently, numerous authors studied the oligo-metastasis concept, where the metastasis are limited in number and sites involved, and that could benefit from an aggressive approach of these lesions, for instance with the help of stereotactic radiotherapy. Nevertheless, there is no clear consensus existing for the time being for the treatment of these tumors. Three main clinical situations can be distinguished: oligo-metastasis state de novo at diagnosis (synchronous) or as first metastatic event of an initially locally limited affection (metachronous); oligo-progression during systemic treatment of a pluri-metastatic disease; and finally oligo-persistence of some remaining metastatic lesions at the nadir of the systemic therapy effect. In this review, we will discuss the place of stereotactic radiotherapy in the treatment of non-small-cell oligo-metastatic oncogene-addicted cancers treated with targeted therapies, differentiating these three main clinical situations. In all these indications, this technique could provide a benefit in terms of local control, possibly even in specific survival, when associated with targeted therapy continuation, related to local control of the oligo-metastatic cerebral or extracerebral lesions. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer remains a leading cause of morbidity and mortality in Poland and globally. The objective of the study was to assess lung cancer incidence among elderly patients in Poland, including data for urban and rural populations, with trend analysis between 2008 and 2012. Material and methods: Differences between lung cancer prevalence in the Polish population aged 65 years or older were assessed with respect to province, gender, and rural vs. urban areas during the 2008-2012 period. Data were extracted from the Polish National Health Authority and Statistical Bureau databases. Results: Lung cancer morbidity among the elderly increased by 14.05% in urban areas but only by 4.01% in rural areas. A 22.41% overall increase was noted in the elderly female population, compared to a 7.29% increase among men aged 65 years and over. Regional differences in morbidity were observed. Conclusions: The rationale behind the differences is likely to be multi-factorial. A change in risk factor exposure in the past is probably now being reflected in lung cancer morbidity. The difference between sexes can potentially be regarded as an unfortunate side-effect of increasing female empowerment. Urban vs. rural, as well as regional, variances are probably due to a multitude of factors, including differences in socio-economic status. [ABSTRACT FROM AUTHOR]

Introduction: 4D-MRI, compared to 4D-CT, provides better soft-tissue contrast for target delineation. However, motion artefacts are often observed due to residual breathing variations. This study is to present a retrospective 4D-MRI reconstruction method based on 2D diaphragm profiles to improve the quality of 4D-MR images in the presence of significant breathing variations.Methods: The proposed 4D-MRI reconstruction method utilized diaphragm profiles (2D cine images on a single sagittal plan at the peak diaphragm) in conjunction with 4D-MR scans (2D-cine images on multiple pre-determined coronal planes along the anterior-posterior direction over a volume of interest). The diaphragm profile images were exploited to sort the 4D-MR scans by matching respiratory amplitude of diaphragm on the 4D-MR scans to the diaphragm profiles. To evaluate reconstructed 4D-MR images (ten 3D-MR images), sagittal images on ten 3D-MR images under free breathing (FB) and respiratory guidance (GB) were compared with diaphragm profile images (reference) from 13 healthy volunteers.Results: Forty-four 4D-MR scan datasets were successfully reconstructed without distinct respiratory-related motion artefacts even with the presence of breathing variation. The differences in diaphragm profiles between the reference and corresponding reconstructed images in the mean of root mean square were similar between FB (3.5 mm) and GB (3.0 mm), confirming that the 4D-MRI reconstruction method was effective even with significant breathing variation.Conclusions: The diaphragm profiles were utilized to reconstruct 4D-MR images with spatial reliability and a fixed scan time under FB and GB. Our method can provide reliable 4D information of thoracic and abdominal regions for MRI-guided radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR–TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6–12 months. It has been demonstrated that autophagy plays an important role in EGFR–TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib. We show that the induction of autophagy in response to icotinib contributes to the development of icotinib resistance. Rg3 is capable of inhibiting autophagic flux and enhancing the sensitivity of NSCLC cells to icotinib. The resistance to icotinib could also be reversed through Rg3-induced autophagy inhibition. Autophagy inhibition by Rg3 increases the therapeutic response in both icotinib-sensitive and icotinib-resistant NSCLC cells with an EGFR-activating mutation and may be an effective new treatment strategy for this disease. [ABSTRACT FROM AUTHOR]

Aims: Telepathology uses digitised image transfer to allow off‐site reporting of histopathology slides. This technology could facilitate the centralisation of pathology services, which may improve their quality and cost‐effectiveness. The benefits may be most apparent in frozen section reporting, in which turnaround times (TATs) are vital. We moved from on‐site to off‐site telepathology reporting of thoracic surgery frozen section specimens in 2016. The aim of this study was to compare TATs before and after this service change. Methods and results: All thoracic frozen section specimens analysed 4 months prior and 4 months following the service change were included. Demographics, operation, sample type, time taken from theatre, time received by laboratory, time reported by laboratory, TAT, frozen section diagnosis, final histopathological diagnosis and final TNM staging were recorded. The results were analysed with spss statistical software version 24. In total, there were 65 samples from 59 patients; 34 before the change and 31 after the change. Specimens included 51 lung, six lymph node, three bronchial, three chest wall and two pleural biopsies. Before the change, the median TAT was 25 min [interquartile range (IQR) 20–33 min]. No diagnoses were deferred. No diagnoses were changed on subsequent paraffin analysis. After the change, with the use of digital pathology, the median TAT was 27.5 min (IQR 21.75–38.5 min). This difference was not significant (P = 0.581). Diagnosis was deferred in one case (3.23%). There was one (3.23%) mid‐case technical failure resulting in the sample having to be transported by courier, resulting in a TAT of 106 min. No diagnoses were changed on subsequent paraffin analysis. Conclusions: There was no significant difference in reporting times between digital technology and an on‐site service, although one sample was affected by a technical failure requiring physical transportation of the specimen for analysis. Our study was underpowered to detect differences in accuracy. [ABSTRACT FROM AUTHOR]

Abstract Lung Adenocarcinoma (LUAD) is the most common cause of lung cancer-related deaths. Long non-coding RNAs (LncRNAs) play an essential role in cancer development and progression. In this study, we identified PILAR1, a prognostic and overexpressed LncRNA, using multiple independent datasets of LUAD patients. Higher expression of PILAR1 was associated with survival in Dhanasekaran et al. (HR = 2.29, p-value = 0.017), TCGA (HR = 1.51, p-value = 0.017) and KM plotter (HR = 2.67, p-value ≤ 0.0001) cohorts. Mutational landscape of LUAD showed that KEAP1 mutation was exclusively present in PILAR1 expressing samples. Further, knockdown of PILAR1 significantly inhibited cell proliferation, colony formation and migration of A549 cells. Importantly, inhibition of PILAR1 made the A549 cells more sensitive to etoposide. Furthermore, pathway analysis using differentially expressed genes in PILAR1 knockdown cells compared to control cells identified enrichment of DNA repair genes suggesting towards the mechanism of PILAR1 mediated etoposide sensitivity. Taken together, we identified a prognostically robust LncRNA, PILAR1, which also regulates cell growth in lung cancer cells. PILAR1 expression identified a novel subtype of LUAD patients with the exclusive KEAP1 mutation. Highlights • PILAR1 is overexpressed in LUAD patients. • PILAR1 is strongly associated with survival of LUAD patients. • KEAP1 mutation is exclusively associated with patients with high PILAR1 expression. • PILAR1 regulates lung cancer cell growth and chemosensitivity. [ABSTRACT FROM AUTHOR]

Abstract Molecular markers are urgently needed to select non-small cell lung cancer (NSCLC) patients most likely to benefit from platinum-based chemotherapies. Of particular interest are proteins that can be found in biofluids like sputum for non-invasive detection. Therefore, we profiled the secretomes of 6 NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2610 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins. Stringent statistical analysis and quantitative filtering yielded 58 biomarker candidates, 34 of which could be detected in clinical biofluids of lung cancer patients such as sputum using label-free LC-MS/MS-based proteomics. To assess performance of these biofluid biomarker candidates, we correlated protein expression with patient survival using a publically available clinical gene expression data set (GSE14814). We thus identified 3 top candidates with potential predictive value in determining cisplatin response (UGGT1, COL6A1 and MAP4) for future development as non-invasive biomarkers to guide treatment decisions. Significance Platinum-based chemotherapies are still the standard of care for NSCLC and other lung cancer types in the clinic today. However, due to chemoresistance, many patients suffer from the toxic side effects of these treatments without gaining any benefit in terms of survival. To date, no molecular biomarkers are available to predict clinical outcome of platinum-based chemotherapy. Because proteins present the functional read-out of genetic, epigenetic and translational events in the cell, a protein test is likely to be particularly suitable for response prediction. Of high relevance are proteins that are shed or secreted from cells, for example at primary tumor sites, and can be found in easily accessible biofluids like sputum for non-invasive detection. Here, we report the proteome profiling of the conditioned media (secretomes) of a panel of NSCLC cell lines in relation to cisplatin IC50 values, as a pre-clinical model, and of patient sputum as a clinical, lung cancer relevant biofluid. Using this approach in conjunction with exploration of the predictive potential in a transcriptome lung cancer patient dataset, we reveal biofluid biomarker candidates that, with further validation, may be used for non-invasive cisplatin response prediction in the future. Graphical abstract Unlabelled Image Highlights • Label-free GeLC-MS/MS-based proteomics on secretomes of human NSCLC cell line panel • 304 differentially expressed proteins between cisplatin sensitive and resistant cells • Striking differences in biology of protein secretion revealed by SecretomeP/SignalP • Detectability of candidate cisplatin response markers in sputum and other biofluids • 3 top biofluid candidates with potential predictive value in transcriptome data [ABSTRACT FROM AUTHOR]

Abstract Tartrate-resistant acid phosphatase 5a (TRACP5a) is mainly secreted by activated macrophages in chronic inflammation. Serum TRACP5a is associated with symptom distress in lung cancer patients during chemotherapy. Therefore, this study aimed to investigate whether chemotherapy drugs modulate TRACP5a as an inducible marker for symptom distress in lung cancer patients during chemotherapy. In clinical analysis, lung cancer participants completely received the six-cycle chemotherapy process (n = 42). Clinical determinations for TRACP5a, C-reactive protein (CRP), interleukin-6 (IL-6), white blood cells, monocytes, and hemoglobin were analyzed at six time points: BL, C1d8, C2d1, C4d1, C4d8, and Ed28. Meanwhile, five questionnaires for fatigue, sleep disturbance, pain, depression, and confusion were finished before drug treatment. For monocyte-to-macrophage differentiation, THP-1 cells were treated with phorbol 12-myristate 13-acetate (PMA). TRACP5a secretion in THP-1 cells was determined at the following days up to 6 days after 1-day incubation of chemotherapy drugs by dot blotting. Clinical analysis revealed that TRACP5a significantly increased at C1d8 and C4d8, but dropped at C2d1 and Ed28. CRP and IL-6 displayed a broad-range variation, resulting in no significant difference among the assessment time points. In contrast, monocytes decreased at C1d8 and C4d8, but rose again at C2d1 and Ed28. In symptom distress, the changes only in fatigue and sleep disturbance were positively associated with the trend in TRACP5a. In PMA-treated THP-1 cells, TRACP5a significantly increased after stimulation with gemcitabine and paclitaxel. Taken together, induction of TRACP5a by chemotherapy drugs might be generated from monocyte-differentiated macrophages, further causing clinical symptom distress in lung cancer patients. [ABSTRACT FROM AUTHOR]

Background. Histidine-rich glycoprotein (HRG) displays anticoagulant and antifibrinolytic properties in animal models, but its effects in humans are unclear. We investigated serum HRG levels and their associations with the disease stage and prothrombotic alterations in lung cancer (LC) patients. Methods. In 148 patients with advanced LC prior to anticancer therapy (87 non-small-cell LC and 61 small-cell LC) versus 100 well-matched controls, we measured HRG levels in association with clot permeability (Ks), clot turbidimetry (lag phase and maximum absorbance), and clot lysis time (CLT). Results. Compared to controls, LC patients had 45.9% lower HRG levels with no associations with demographics and comorbidities. Decreased HRG, defined as the 90th percentile of control values (<52.7 μg/ml), was 16 times more common in subjects with than without LC (OR=16.4, 95% CI 9.2-23.5, p<0.01). HRG<38 μg/ml discriminated stage IIIAB/limited disease from IV/extensive disease (ED) LC. In LC patients, HRG correlated inversely with CLT (r=−0.41, p<0.001), but not with other fibrin variables. Among stage IV/ED LC, HRG correlated significantly with Ks and lag phase (r=0.28 and r=0.33, respectively, both p<0.001). LC patients with low Ks (10th percentile of control values) combined with prolonged CLT (90th percentile of control values) had reduced HRG levels compared to the remainder (p=0.003). No such observations were noted in controls. Conclusions. Our study is the first to show that decreased HRG levels occur in advanced LC and are associated with the disease stage and hypofibrinolysis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • This review focuses on the early detection of lung cancer biomarkers. • Latest biosensing approaches for lung cancer detection studies are addressed. • Conventional methods for lung cancer biomarkers detection are also summarized. Abstract Lung cancer is undoubtedly one of the most serious health issues of the 21 st century. It is the second leading cause of cancer-related deaths in both men and women worldwide, accounting for about 1.5 million deaths annually. Despite advances in the treatment of lung cancer with new pharmaceutical products and technological improvements, morbidity and mortality rates remains a significant challenge for the cancer biologists and oncologists. The vast majority of lung cancer patients present with advanced-stage of pathological process that ultimately leads to poor prognosis and a five-year survival rate less than 20%. Early and accurate screening and analysis using cost-effective means are urgently needed to effectively diagnose the disease, improve the survival rate or to reduce mortality and morbidity associated with lung cancer patients. Thus, the only hope for early recognition of risk factors and timely diagnosis and treatment of lung cancer is biosensors technology. Novel biosensing based diagnostics approaches for predicting metastatic risks are likely to have significant therapeutic and clinical impact in the near future. This article systematically provides a brief overview of various biosensing platforms for identification of lung cancer disease biomarkers, with a specific focus on recent advancements in electrochemical and optical biosensors, analytical performances of different biosensors, challenges and further research opportunities for routine clinical analysis. [ABSTRACT FROM AUTHOR]

The period of recovery following a lung-cancer surgery presents unique challenges and psychological demands. The study utilized ecological momentary assessments (EMA) to repeatedly sample mindfulness states in a sample of mindfulness-untrained individuals following hospital discharge. Intra- and inter- individual variability was assessed to examine cancer patients' natural capacity to exhibit mindfulness states during two weeks of recovery. Fifty nine stage I lung cancer patients (61% women, mean age = 66.1, SD = 7.9) completed EMA twice a day for two weeks. Mean level of mindfulness in the sample was low and equaled.49 (SD = .51) on the 5 point scale, with older participants being less likely to endorse mindful states. Net variability in mindfulness, defined as the person-based standard deviation in momentary scores, equaled.42 (SD = .26), ranging for 0 to 1.3 and indicating very modest variability for most participants. Results of the multi-level variance partitioning model revealed 41.4% of variance in mindfulness scores at the inter-individual, 2.4% on the temporal (i.e.,.2% weekly and 2.2% daily), and 56.2% on the momentary levels. Findings indicate that, for cancer patients recovering from surgery, the innate ability to exhibit mindfulness is limited. From the methodological standpoint, consideration of intra-individual variability has implications for conceptualization and design of EMA studies. [ABSTRACT FROM AUTHOR]

The paper is motivated by the problem of comparing the accuracy of two molecular tests in detecting genetic mutations in tumor samples when there is no gold standard test. Commonly used sequencing methods require a large number of tumor cells in the tumor sample and the proportion of tumor cells with mutation positivity to be above a threshold level whereas new tests aim to reduce the requirement for number of tumor cells and the threshold level. A new latent class model is proposed to compare these two tests in which a random variable is used to represent the unobserved proportion of mutation positivity so that these two tests are conditionally dependent; furthermore, an independent random variable is included to address measurement error associated with the reading from each test, while existing latent class models often assume conditional independence and do not allow measurement error. In addition, methods for calculating the sample size for a study that is sufficiently powered to compare the accuracy of two molecular tests are proposed and compared. The proposed methods are then applied to a study which aims to compare two molecular tests for detecting EGFR mutations in lung cancer patients. [ABSTRACT FROM AUTHOR]

Chemometric method of uncorrelated linear discriminant analysis (ULDA) was applied to the data of amino acid levels in serum of lung cancer patients and healthy people, eventually successfully classifies the samples of cancer patients and healthy people. Simultaneously, several potential amino acid biomarkers were possibly chosen. So the method of amino acid levels combined with ULDA algorithm could be applied to the identification of cancer and exploration of tumor biomarker, which has certain practical value and application prospects. [ABSTRACT FROM AUTHOR]

Purpose: Improving the coordination of care for people with lung cancer is a health priority. This study aimed to tailor an existing care coordination survey for a lung cancer population, investigate coordination experiences for patients who had received hospital-based treatment and identify any factors that may be associated with poor care coordination.Methods: We conducted a cross-sectional survey of lung patients within two tertiary hospitals in Sydney, Australia. The Cancer Care Coordination Questionnaire for Patients (CCCQ-P) is a psychometrically valid and reliable survey originally developed for colorectal cancer. We pilot tested a survey adaptation with lung cancer patients, support group members and medical specialists (n = 49). A revised survey was mailed to eligible patients via their medical specialist.Results: Fifty-three of 118 eligible participants (45%) completed the CCCQ-P; most had early-stage disease and were about 70 years old. Overall, participants reported positive experiences of care coordination (mean total score 78.1), with high scores on communication and navigation subscales. The most problematic areas related to administrative aspects of care coordination and communication and information provision. Two patient groups (those residing in regional and rural areas, or no experience with the health system prior to diagnosis) reported significantly lower scores on the navigation subscale.Conclusions: This study found that lung cancer patients' experience of care coordination was positive, but highlighted the need for strategies to assist patients living in rural areas, and those with no experience of the health care system. The CCCQ-P survey instrument can be used in future lung cancer studies. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 46-year-old male patient with a two-year history of lung cancer and was treated for a Port-A-Cath silent embolization to his left distal pulmonary artery. Topics discussed include the percutaneous retrieval approach, the Chest X-ray results, and the risk of fracture and distal embolization toward the patient's heart.

Background: This randomized phase 2 trial compared the efficacy and safety of second-line nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without the addition of CC-486 (an oral formulation of 5-azacytidine) in patients with advanced-stage, nonsquamous non-small cell lung cancer.Methods: Patients were randomized to receive either nab-paclitaxel 100 mg/m2 on days 8 and 15 plus CC-486 200 mg daily on days 1 to 14 or single-agent nab-paclitaxel 100 mg/m2 on days 1 and 8, with both regimens administered every 21 days until tumor progression or unacceptable toxicity. The primary endpoint was progression-free survival. Secondary endpoints included the overall response rate, the disease control rate, and overall survival.Results: Between January 2015 and August 2016, 161 patients were randomized (81 to the combination arm and 80 to the single-agent nab-paclitaxel arm). There was no benefit from the addition of CC-486 to nab-paclitaxel. The median progression-free survival was 3.2 months for the combination and 4.2 months for single-agent nab-paclitaxel (hazard ratio, 1.3; 95% confidence interval, 0.9-1.9). The median overall survival was 8.1 months in the combination arm and 17 months in the single-agent nab-paclitaxel arms (hazard ratio, 1.7; 95% confidence interval, 1.08-2.57). Grade 3 or greater treatment-related, emergent adverse events were reported by 40.5% of patients in the combination arm and by 31.6% of those in the single-agent nab-paclitaxel arm.Conclusions: Single-agent nab-paclitaxel was associated with promising outcomes and a tolerable safety profile as second-line treatment for patients with advanced-stage, nonsquamous non-small cell lung cancer. There was no benefit from the addition of CC-486 to nab-paclitaxel. [ABSTRACT FROM AUTHOR]

Recent trials have demonstrated that the addition of a programmed cell death protein 1 inhibitor to chemotherapy in the first‐line setting in patients with metastatic squamous or nonsquamous non–small cell lung cancer improves survival compared with chemotherapy alone. These findings provide a new treatment option for patients with newly diagnosed, advanced non–small cell lung cancer, regardless of tumor histology or programmed death‐ligand 1 expression, thereby representing a major advancement in the field. [ABSTRACT FROM AUTHOR]

Purpose: Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [18F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue.Procedures: Seventy-two patients with histologically proven lung cancer and adjacent atelectasis were investigated. Non-contrast-enhanced [18F]FDG-PET/CT was performed within 2 weeks before surgery/biopsy. Boundaries of the primary within the atelectasis were determined visually on the basis of [18F]FDG uptake; CT density was quantified manually within each primary and each atelectasis.Results: CT density of the primary (36.4 Hounsfield units (HU) ± 6.2) was significantly higher compared to that of atelectatic lung (24.3 HU ± 8.3; p < 0.01), irrespective of the histological subtype. The discrimination between different malignant tumors using density analysis failed. SUVmax was increased in squamous cell carcinomas compared to adenocarcinomas. Irrespective of the malignant subtype, a possible cutoff value of 24 HU may help to exclude the presence of a primary in lesions below 24 HU, whereas a density above a threshold of 40 HU can help to exclude atelectatic lung.Conclusion: Density measurements in patients with lung cancer and surrounding atelectasis may help to delineate the primary tumor, irrespective of the specific lung cancer subtype. This could improve T staging and radiation treatment planning (RTP) without additional application of a contrast agent in CT, or an additional magnetic resonance imaging (MRI), even in cases of lung tumors of neuroendocrine differentiation or in slowly growing tumors with less avidity to [18F]FDG. [ABSTRACT FROM AUTHOR]

Aims: The aims of the current study were: (i) to examine the prescribing of preventative medication in a cohort of people with advanced lung cancer on hospital admission and discharge across different healthcare systems; and (ii) to explore the factors that influence preventative medication prescribing at hospital discharge. Methods: A retrospective cohort study was conducted across two centres in the UK and the US. The prescribing of preventative medication was examined at hospital admission and discharge for patients who died of lung cancer. A zero‐inflated negative binomial regression model was used to examine the association between preventative medications at discharge and patient‐ and hospital‐based factors. The classes of preventative medication prescribed included were: vitamins and minerals, and antidiabetic, antihypertensive, antihyperlipidaemic and antiplatelet medications. Results: In the UK site (n = 125), the mean number of preventative medications prescribed was 1.9 [standard deviation (SD) 1.7) on admission, and 1.7 (SD 1.7) on discharge, and in the US site (n = 191) the mean was 2.6 (SD 2.2) on admission and 1.9 (SD 2.2) on discharge. The model found a significant association between the number of preventative drugs prescribed on admission and the number on discharge; it also found a significant association between the total number of drugs prescribed on discharge and the number of preventative medications on discharge. Other indicators related to patient and hospital factors were not significantly associated with the number of preventative medications supplied on discharge. Conclusions: The use of preventative medication was common in lung cancer patients, despite undergoing discharge. Patient‐ and hospital‐based factors did not influence the prescribing of preventative medication. [ABSTRACT FROM AUTHOR]

Introduction Mortality following surgery for lung cancer increases at 90 days. The objective of this study was to determine the rate, factors, time to death, hospital stay until discharge, time to death after discharge and causes of mortality at 90 days following surgery for lung cancer. Methods A prospective follow-up study was performed in a cohort of 378 patients who underwent surgery for lung cancer between January 2012 and December 2016. Data on preoperative status, postoperative complications, and mortality were collected. Results Rates of mortality were 1.6% vs. 3.2% at 30 and 90 days, respectively. Half of deaths occurred between 31 and 90 postoperative days following discharge. The variables found to be related to mortality at 90 days were a Charlson Index >3 (p < 0.001), a history of stroke (p = 0.036), postoperative pneumonia (p = 0.001), postoperative pulmonary or lobar collapse (p = 0.001), reintubation (p < 0.001) and postoperative arrhythmia (p = 0.0029). The risk of mortality was also observed to be associated with the type of surgical technique -being higher for thoracotomy as compared to video-assisted thoracoscopy (VATS) (p = 0.011) -, and hospital readmission after discharge (p < 0.001). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Multivariate analysis revealed that a Charlson Index >3 (p = 0.001) OR 2.0 (1.55,2.78), a history of stroke (p = 0.018) OR 5.1 (1.81, 32.96) and postoperative pulmonary or lobar collapse (p = 0.001) OR 8.5 (2.41,30.22) were independent prognostic factors of mortality. The most common causes of death were related to respiratory (58.3%) and cardiovascular (33.2%) complications. Conclusions Mortality at 90 days following surgery for lung cancer doubles 30-day mortality, which is a relevant finding of which both, patients and healthcare should be aware. Half the deaths within 90 days after surgery for lung cancer occur after discharge. Specific outpatient follow-up programs should be designed for patients at a higher risk of 90-day mortality. [ABSTRACT FROM AUTHOR]

Background: Squamous cell lung cancer (SqCLC) is a distinct histologic subtype of non-small cell lung cancer (NSCLC). Although the discovery of driver mutations and their targeted drugs has remarkably improved the treatment outcomes for lung adenocarcinoma, currently no such molecular target is clinically available for SqCLC. The CDKN2A locus at 9p21 encodes two alternatively spliced proteins, p16INK4a (p16) and p14ARF (p14), which function as cell cycle inhibitors. The Cancer Genome Atlas (TCGA) project revealed that CDKN2A is inactivated in 72% of SqCLC cases. In addition, it was found that CDKN2A mutations are significantly more common in SqCLC than in adenocarcinoma. Down-regulation of p16 and p14 by CDKN2A gene inactivation leads to activation of cyclin-dependent kinases (CDKs), thereby permitting constitutive phosphorylation of Rb and subsequent cell cycle progression. Here, we hypothesized that CDK inhibition may serve as an attractive strategy for the treatment of CDKN2A-defective SqCLC.Methods: We investigated whether the CDK inhibitors flavopiridol and dinaciclib may exhibit antitumor activity in CDKN2A-defective SqCLC cells compared to control cells. The cytotoxic effect of the CDK inhibitors was evaluated using cell viability assays, and the induction of apoptosis was assessed using TUNEL assays and Western blot analyses. Finally, anti-tumor effects of the CDK inhibitors on xenografted cells were investigated in vivo.Results: We found that flavopiridol and dinaciclib induced cytotoxicity by enhancing apoptosis in CDKN2A-defective SqCLC cells, and that epithelial to mesenchymal transition (EMT) decreased and autophagy increased during this process. In addition, we found that autophagy had a cytoprotective role.Conclusion: Our data suggest a potential role of CDK inhibitors in managing CDKN2A-defective SqCLC. [ABSTRACT FROM AUTHOR]

Purpose: Neuroendocrine tumors of the lung (LNETs) encompass a heterogeneous group of lesions, including tumors with no or low metastatic potential, such as typical (TCs) and atypical (ACs) carcinoids, and highly aggressive neuroendocrine carcinomas. To date, only a few biomarkers with prognostic impact have been identified in LNETs. Previous experimental studies have suggested that the cytokine CXCL12 might have a role in stratifying the outcome of lung cancer as well as LNET patients. However, the reliability of immunohistochemical (IHC) tissue expression of CXCL12 in evaluating the prognosis of resected LNETs is currently not known.Methods: Here, we subjected a cohort of 112 resected LNETs specifically enriched for ACs to IHC for CXCL12 and Ki67 using routine procedures. The clinical value of CXCL12 was assessed by applying the Cox proportional-hazards model to overall and disease-free survival rates.Results: We found that CXCL12 was expressed in 8.3 to 38% of LNETs, depending on the different diagnostic categories. Upon survival analysis, when considering the whole cohort, we found that CXCL12-positive cases exhibited shorter disease-free survival rates compared to CXCL12-negative cases. Among ACs, tumors overexpressing CXCL12 showed significantly shorter disease-free survival rates. Finally, we found that the Ki67 index in ACs was higher in the CXCL12-positive cases.Conclusion: CXCL12 immunohistochemistry may serve as a potentially useful tool to better stratify LNETs, and more specifically ACs, in clinical practice. [ABSTRACT FROM AUTHOR]