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Lung cancer and chronic obstructive pulmonary disease share common risk factors and the same pathophysiological mechanisms, which are a common comorbidities and interact with each other. At present, there is no universal standard for diagnosis and treatments, and these patients have a poor prognosis. Pulmonary function detection and regular low-dose spiral CT can improve the diagnosis rate of the comorbid disease. The principle of "co-morbidities, co-treatment of cancer and lung disease" should be fully considered in the process of diagnosis and treatment.

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95% CI : 5.5-6.4 months), and the median OS was 17.0 months (95% CI : 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95% CI : 6.0-7.9 months) vs 4.0 months (95% CI : 3.3-4.6 months), P <0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95% CI : 18.1-19.9 months) vs 13.0 months (95% CI : 10.8-15.1 months), P <0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis ( HR =1.414, 95% CI : 1.253-1.725), non-first-line dual immunotherapy ( HR =1.412, 95% CI : 1.184-1.652), and tumor mutation burden<10 mut/Mb ( HR =1.328, 95% CI : 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma ( HR =0.917, 95% CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) respond well to ALK tyrosine kinase inhibitors (TKIs), and echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged NSCLC accounts for the majority of those patients. However, few studies have evaluated ALK-TKIs treatment for patients with huntingtin-interacting protein 1 (HIP1)-ALK fusions. This retrospective study evaluated the clinicopathological characteristics, genomic features, response to ALK-TKIs, and resistance mechanisms in 11 cases with HIP1-ALK fusions from five Chinese centers. Patients who received crizotinib at the Chinese centers had an objective response rate of 90% [9/10 cases, 95% confident index (CI): 54.1%-99.5%], median progression-free survival of 17.9 months (95% CI: 5.8-NA months), and median overall survival of 58.8 months (95% CI: 24.7-NA months). One patient who received first-line lorlatinib treatment achieved partial response for > 26.5 months. Despite the small sample size, HIP1-ALK (H21:A20) variant was the most common variant (four of 11 cases, 36.4%) and associated with better outcomes. Among the 11 cases, there were eight patients having available specimens for genetic testing before ALK-TKIs treatment and four patients undergoing biopsy after ALK-TKIs failure. The most common coexisting gene was TP53 among 11 patients and two of four patients after crizotinib failure harbored acquired ALK mutations (e.g., L1152V/Q1146K and L1196M). Brigatinib treatment appeared to be effective for a patient who failed crizotinib treatment because of the L1152V/Q1146K mutations, which might be related to increased binding affinity to these mutants. Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation. Larger studies are needed to evaluate the significance of HIP1-ALK-rearranged NSCLC., (© 2021 Wiley Periodicals LLC.)

Objective: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC., Methods: A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed., Results: Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23-74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75-73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5-26.7 months)., Conclusions: Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.

Objective: To explore whether combining treatment of chronic obstructive pulmonary disease (COPD) with anti-tumor therapy is better than that of tumor treatment alone in advanced non-small cell lung cancer (NSCLC) patients with COPD in the real world. Methods: The clinical data of 101 patients with advanced NSCLC complicated with COPD from January 1, 2015, to December 31, 2017, in the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively, including 99 males and two females, aged from 52 to 84 years[average (67±8) years]. Among the patients, 90 (89.1%) were smokers, with an average pack-year smoking index of (47±4) . The patients were divided into observation and control groups, depending on whether they received standardized anti-COPD supportive treatment. In the observation group, there were 36 patients, including 35 males and one female, aged from 54 to 84 years[ average (67±8) years], with an average pack-year of smoking (47±4). There were 65 patients in the control group, including 64 males and one female, aged from 52 to 83 years [average (67±8) years], with an average pack-year of smoking 47±4. There was no significant difference in the baseline data between the two groups. The primary outcome measures included the Objective response rate (ORR), disease control rate (DCR), disease-free survival (PFS), and overall survival (OS) of the two groups. An unpaired t -test was used to compare continuous variables between the observation and control groups. The Pearson chi-square test was used to compare categorical variables between the two groups. Kaplan-Meier survival curves were used to evaluate the median PFS and median OS of patients, and the log-rank test was used to assess differences between groups. Result: The ORR of the observation group and the control group was 22.6% (7 cases) and 22.2% (11 cases), respectively, with no significant difference (χ(2)=0.01, P= 0.971). The DCR between the observation group and the control group was 58.1% (19 cases) and 57.8% (27 cases), with no significant difference (χ(2)=0.02, P= 0.889). Median PFS in the observation group was 6.0 months, which was better than the 3.5 months in the control group (χ(2)=3.947, P< 0.05). The median OS of the observation group was 18.0 months, which was better than the 15.0 months of the control group (χ(2)=4.083, P< 0.05). Conclusions: Compared with the treatment of tumors alone, combination of anti-tumor therapy with anti-COPD therapy showed longer PFS and OS in patients with advanced NSCLC complicated with COPD.

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.

Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harborin g in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harborin g in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR , thus having no effect on the interaction between gefitinib and EGFR .

Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO(2) improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion: Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.

Surface-enhanced Raman spectra of natural tissue and cancerous tissue of lung from 300 to 1700 cm(-1) were measured. In the cancerous tissue of lung, the orderly conformations of amides III and amides I of the main chains in protein such as alpha-helix, beta-corner and no rules curly were damaged seriously; conversely, the extendable vibration of skeleton C-N and skeleton C-C increased. Side chains change became complicated. In general, the content of nucleic acids increases in the cancer tissue of lung. The lengthways conformations of lecithoid chains is out-of-order in the cancerous tissue of lung compared with the natural ones.

Objective: To investigate the blood supply of primary lung cancer (PLC) using CT angiography for bronchial artery (BA) and pulmonary artery (PA)., Methods: Thin-section enhanced multi-layer spiral CT (MSCT) were carried out in 147 primary lung cancer patients and 46 healthy subjects as control. Three-dimensional images of bronchial artery and pulmonary artery were obtained using volume render (VR) and multi-planar reconstruction (MPR) or maximum intensity projection (MIP) at the workstation, and their morphological findings and relationship with the mass were assessed., Results: 136 primary lung cancer patients and 32 healthy controls were evaluated for at least one bronchial artery displayed clearly in VR. The detective rate of the bronchial artery was 92.5% and 69.6%, respectively. The bronchial artery caliber and the total section area of lesion side in lung cancer patients were significantly larger than that on the contralateral side and that of the control (P < 0.05). Bronchial artery on the lesion side in lung cancer was dilated and tortuous, directly penetrating into the mass with reticularly anastomosed branches. In the PLC patients, all PA were shown clearly with normal morphological image though crossing over the masses in 54 patients; In 25 PLC patients, the PA being essentially intact, was pushed around and surrounded the mass, giving the "hold ball" sign; In 40 other PLC patients, PA being also intact, the mass surrounded and buried the PA from the outside, crushing the PA flat resulting in an eccentric or centrifugal shrinkage, forming the "dead branch" sign; In the rest 28 patients, the PA was surrounded and even compressed, forming the "residual root" sign., Conclusion: Primary lung cancer patient shows dilated bronchial arteries and increased bronchial artery blood flow, whereas pulmonary arteries just pass through the mass or are compressed by the mass. It is further demonstrated that the bronchial artery, instead of the pulmonary artery, is the main vessel of blood supply to the primary lung cancer as shown by MSCT angiography of bronchial artery and pulmonary artery.

Objective: To investigate the relationship between p53 mutation and the expression of some drug-resistance genes commonly found in lung cancer., Methods: Sixty-six of untreated lung cancers and paracancerous tissues were obtained by surgical resection. Immunohistochemical staining was employed for detection of both mutant p53 and drug-resistance associated proteins (MDR1, MRP1, LRP, TOPO II alpha, GST-pi), PCR-SSCP and RT-PCR were used for detection of mutations of p53 exon 5-8 as well as the expression of mRNAs for the genes coding those drug-resistance associated proteins in 31/66 cases. ATP-TCA assay was also performed simultaneously in 12 out of the 31 cases for evaluation of their reaction in response to chemotherapy., Results: Correlations were found between p53 mutation and expression of either Pgp or MRP1 or GST-pi (P < 0.05). There was a significant correlation between p53 mutation with simultaneous expression of Pgp and MRP1 and drug-resistance to either vinorelbine or carboplatin., Conclusions: The results suggested that p53 mutation in lung cancers was closely correlated with the expression of drug-resistance associated protein which was associated with endogenous resistance to most of chemotherapeutic drugs. It indicated that wild p53 gene therapy might be helpful for treating the endogenous drug resistance of lung cancer in chemotherapeutics.