Squamous Cell Lung Cancer Research Articles

A causal association between chemokines and the risk of lung cancer: a univariate and multivariate mendelian randomization study

BackgroundObservational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, and treatment. However, few studies have examined the causal association between them.MethodsSummary data of chemokines and lung cancer were obtained from genome-wide association studies. Mendelian randomization (MR) analyses were performed by five methods, Inverse variance weighted (IVW), Weighted median estimation, MR-Egger, Simple mode and Weighted, with IVW as the primary analysis method. Sensitivity analysis was used to assess the reliability of the MR results. Multivariate Mendelian randomization studies were used to infer whether causality was influenced by potential mediators. The expression levels of CCL21 were analyzed by quantitative real-time PCR.ResultsWe found that CCL21 was negatively associated with lung adenocarcinoma risk. CCL25 was positively associated with lung squamous cell carcinoma risk. CCL5 was negatively associated with small cell lung cancer risk. CCL21, CCL24, CCL27, and CCL28 was positively associated with small cell lung cancer risk. After multivariate Mendelian randomization adjustment for smoking behavior, it was found that the effect of CCL25 on lung squamous cell cancer disappeared, and the effect of CCL21 on small cell lung cancer was quite opposite to the univariate. The receiver operating characteristic curve indicated that chemokines had high accuracy in the diagnosis of lung cancer. CCL21 expression levels showed large differences in lung adenocarcinoma cells.ConclusionThese results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer.

Successful management of complete heart block in checkpoint inhibitor induced myocarditis by left bundle branch area pacing: a case report

Abstract Background Optimal management of checkpoint inhibitor-induced complete heart block is unknown. Previous reports showed relatively high incidence of pacing failure due to the co-existing myocarditis. Case summary A 71-year-old male with a prior history of stage IV metastatic squamous cell lung cancer presents was admitted for dyspnoea and hypotension 10 days after checkpoint inhibitor treatment using pembrolizumab. He was found to have myocarditis, third-degree AV block, severe left ventricular systolic dysfunction with EF 35%, and required pressure support. A dual chamber pacemaker using left bundle branch area pacing (LBBAP) was urgently placed that immediately improved his haemodynamics. Both the cathode and anode were able to capture the ventricle at different pacing outputs. The patient was taken off all intravenous pressors and successfully transferred to a larger centre for further management of the myocarditis with no further arrhythmia or hypotension. Discussion In conclusion, because of the unique ability to capture a large amount of myocardium from both the tip and ring electrodes as well as the ability to deliver cardiac resynchronization therapy, LBBAP may be the preferred pacing strategy in patients who develop complete heart block due to checkpoint inhibitor-induced myocarditis.

Squamous Cell Lung Cancer Presenting with Initial Rare Paraneoplastic Hematological Findings

Squamous Cell Lung Cancer Presenting with Initial Rare Paraneoplastic Hematological Findings

Non-small cell lung carcinoma. Clinical case

In 2020, 2.2 million new cases of lung cancer were reported. The main form of lung cancer is non-small cell carcinoma (85%). Non-small cell lung cancer has 3 subtypes: adenocarcinoma, large cell and squamous cell carcinoma. Squamous cell lung cancer occurs in 20-40% of all lung cancers. Squamous cell lung cancer is associated with an unfavorable outcome. 5-year survival rate not exceeding 18%.

18F-FDG PET/CT Findings of Isolated Renal Metastasis From Squamous Cell Lung Cancer.

We present the 18F-FDG PET/CT findings of a 64-year-old man with isolated renal metastasis. He had a history of radical surgery for squamous cell lung cancer 14 months ago, followed by chemotherapy and immunotherapy. The renal metastasis presented as a small focus of increased FDG uptake in the restaging 18F-FDG PET/CT scan, which was regarded as renal cortical tracer retention. The renal metastasis was more prominent on the second PET/CT performed 5 months later. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed the diagnosis of renal squamous cell carcinoma metastasis.

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

Living for the Moment - How Important Is It in the End of Life?

This essay investigates the role of present-moment living in end-of-life care, drawing on reflections from a personal patient encounter in a palliative care setting, Mrs. B, a 63-year-old patient with terminal squamous cell lung cancer, whose experience underscores the impact of living with a sense of fulfillment and joy despite a life-limiting diagnosis. Mrs. B's approach to her illness-marked by an optimistic acceptance of mortality and a focus on daily joys-challenges traditional palliative care paradigms that emphasize somberness and future-oriented care. Through detailed narrative and reflective analysis, the essay highlights how Mrs. B's resilience and spiritual beliefs contributed to her ability to maintain a positive outlook in the face of terminal illness. This case study illustrates the potential for joy and present-moment living to coexist with palliative care practices, offering a nuanced perspective on patient care. The discussion extends to the implications for healthcare professionals, advocating for a more adaptable and empathetic approach that aligns with individual patient values and preferences. This reflection calls for a shift in palliative care practices towards recognizing and supporting the diverse ways patients navigate their end-of-life experiences.

Classification of histological subtypes of non-small cell lung cancer using computerized tomography texture analysis

Objective: This study aimed to differentiate between the two main histological subtypes of non-small cell lung cancer using a non-invasive technique, computerized tomography texture analysis. Method: We included 53 patients. All patients were histopathologically proven non-small cell lung cancer cases. All patients underwent thorax CT scans. In CT images, the differences present in the texture features of adenocarcinoma and squamous cell carcinoma, which are the two main histological subtypes of non-small cell lung cancer, were determined by the consensus of two radiologists for computerized tomography-based texture analysis. Results: A total of 44 texture features were extracted, including 12 first-order features and 32 second-order features derived from gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), neighborhood gray-level different matrix (NGLDM), and gray-level zone length matrix (GLZLM) features in 51 CT images. None of the evaluated texture parameters were statistically significant. However, in patients with squamous cell lung cancer, the values of Intensity Histogram, NGTDM Complexity, and Intensity Based Robust Mean Absolute Deviation higher from adenocarcinoma patients and had the highest area under the curve in roc analyses (0.727, 0.664, 0.666 respectively) Conclusion: Intensity Histogram, NGTDM Complexity, and Intensity Based Robust Mean Absolute Deviation features can be used to differentiate between the subtypes of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. These features were highly associated with the high intratumoral heterogeneity of squamous cell lung cancer.

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (>2 cm in diameter, volume >4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume <18.5 cm3 and ≥18.5 cm3 were statistically significant (p<0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

Cancer Incidence among Marines and Navy Personnel and Civilian Workers Exposed to Industrial Solvents in Drinking Water at US Marine Corps Base Camp Lejeune: A Cohort Study.

Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. A cohort cancer incidence study was conducted of Marines/Navy personnel who began service and were stationed at Camp Lejeune () or Camp Pendleton, California () between 1975 and 1985 and civilian workers employed at Camp Lejeune () or Camp Pendleton () between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Individual-level information on primary invasive cancers and in situ bladder cancer diagnosed between 1996 and 2017 was obtained from 54 US cancer registries. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts, adjusted for sex, race, education, and rank (or blue-collar work), with age as the time variable. Precision of aHRs was evaluated using the 95% confidence interval (CI) ratio (CIR). Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 and 1,563, respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 and 1,416, respectively. Compared with Camp Pendleton, Camp Lejeune Marines/Navy personnel had aHRs with CIRs for all myeloid cancers (; 95% CI: 1.03, 1.49), acute myeloid leukemia (; 95% CI: 1.03, 1.85), myelodysplastic and myeloproliferative syndromes (; 95% CI: 1.07, 2.62), polycythemia vera (; 95% CI: 0.94, 2.11), and cancers of the esophagus (; 95% CI: 1.03, 1.56), larynx (; 95% CI: 0.98, 1.50), soft tissue (; 95% CI: 0.92, 1.59), and thyroid (; 95% CI: 1.03, 1.45). Lymphoma subtypes mantle cell and marginal zone B-cell and lung cancer subtypes adenocarcinoma and non-small cell lung cancer also had aHRs with CIRs . Compared with Camp Pendleton, Camp Lejeune civilian workers had aHRs with CIRs for all myeloid cancers (; 95% CI: 0.83, 2.36), squamous cell lung cancer (; 95% CI: 1.10, 2.41), and female breast (; 95% CI: 0.97, 1.52) and ductal cancer (; 95% CI: 1.02, 1.71). Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers exposed to contaminated drinking water at Camp Lejeune compared with Camp Pendleton. https://doi.org/10.1289/EHP14966.

A tumor cornification and immune-infiltration-based scheme for anti-PD-1 plus chemotherapy response in advanced squamous cell lung carcinoma

Anti-PD-1 immunotherapy plus chemotherapy (combo) exhibits significantly prolonged survival for squamous cell lung cancer (LUSC). An exploration of predictive biomarkers is still needed. High-throughput RNA sequencing (RNA-seq) of 349 LUSC samples from the randomized, multi-center, phase 3 trial ORIENT-12 (ClinicalTrials.gov: NCT03629925) was conducted for biomarker discovery, followed by flow cytometry and multiplex immunohistochemistry (mIHC) in additional clinical cohorts, and invitro experiments were performed for verification. A high abundance of activated CD8+ T and CD56bright natural killer (NK) cells benefited patients' outcomes (progression-free survival [PFS]; overall survival [OS]) with combo treatment. Tumor cornification level remarkably affected the infiltration of the two crucial immune cells. Thus, a novel scheme of LUSC immune infiltration and cornification characterization-based classification (LICC) was established for combo efficacy prediction. Patients who received combo treatment achieved significant PFS improvements in LICC1 (hazard ratio [HR]= 0.43, 95% confidence interval [CI]: 0.25-0.75, p= 0.0029) and LICC2 (HR= 0.32, 95% CI: 0.17-0.58, p= 0.0002) subtypes but not in the LICC3 subtype (HR= 0.86, 95% CI: 0.60-1.23, p= 0.4053). Via single-cell RNA-seq analysis, the tumor cornification signal was mainly mapped to SPRR3+ tumor cells, whose relationships with activated CD8+ T or CD56bright NK cells were verified using flow cytometry and mIHC. Our data suggest that SPRR3+ tumor cells might evade immune surveillance via the CD24-SIGLEC10 (M2 macrophage) axis to maintain a suppressive tumor microenvironment. Tumor cornification greatly impacts immune infiltration, and the LICC scheme may guide clinical medication of anti-PD-1+chemo treatment in patients with LUSC. The study was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, Shanghia Multidisplinary Cooperation Building Project for Diagnosis and Treatment of Major Disease, and Innovent Biologics, Inc.

P4.17D.05 Squamous Cell Lung Cancer Still Remains the Most Common Histological Subtype of Lung Cancer in Rural India

P4.17D.05 Squamous Cell Lung Cancer Still Remains the Most Common Histological Subtype of Lung Cancer in Rural India

EP.12E.05 Exploring Clinical Characteristics and Treatment Outcomes of Squamous Cell Lung Cancers Harboring EGFR and ALK Mutations: A Case Series

EP.12E.05 Exploring Clinical Characteristics and Treatment Outcomes of Squamous Cell Lung Cancers Harboring EGFR and ALK Mutations: A Case Series

MA19.10 The Tracerx 421 Cohort Provides Insights to Key Pathological Features of Lung Squamous Cell Cancer

MA19.10 The Tracerx 421 Cohort Provides Insights to Key Pathological Features of Lung Squamous Cell Cancer

Characterization of Non-Small Cell Lung Cancer Tissue by Quantitative Assessment of Class III β-Tubulin Expression

Background. The cytoskeletal protein β-tubulin class III (Tubb3) is associated with tumor resistance to taxanes and vinca alkaloids, as well as with the metastatic potential of neoplasm, however, data from immunohistochemical analysis of Tubb3 expression in non-small cell lung cancer (NSCLC) tissue are few and contradictory. Purpose. Characterization of the level and intensity of Tubb3 expression in NSCLC tissue and analysis of the identified parameters correlation with clinically significant characteristics of the disease. Methods. Quantitative assessment of the level and intensity of Tubb3 expression in 120 surgical samples of NSCLC was carried out by immunofluorescence method associated with flow cytometry. Primary rabbit monoclonal antibodies specific to Tubb3 and secondary anti-rabbit antibodies conjugated with fluorescent dye DyLight650 (ab98510, UK) were used. The expression of the marker was assessed by two parameters: the level of expression measured as the percentage of the cells expressing Tubb3 and the intensity of expression in conventional units (CU) represented as the ratio of the geometric mean fluorescence intensity in the experimental and control samples (cells incubated with secondary antibodies only). Results. 1. Tubb3 expression was detected in all NSCLC samples studied. The median level and intensity of Tubb3 expression was 30.5% and 2.0 CU with significant differences (up to 10 times) in the quantitative values of both parameters in different patients. 2. The distribution of the studied tumors in terms of the level and intensity of Tubb3 expression differs from normal (P<0.001), the associative relationship between the assessed parameters is very strong (Spearman's rank correlation coefficient was 0.91; P<0.0001). 3. Statistical analysis did not reveal correlations between the level of Tubb3 expression and the gender and smoking status of the patients, with the degree of tumor differentiation, as well as with the stage of NSCLC. 4. In the group of lung adenocarcinomas, the median level of Tubb3 expression is higher compared with squamous cell lung cancer in male and female patients (P=0.01). Conclusion. High heterogeneity of Tubb3 expression level in NSCLC tissue in the patients and differences in the parameters between the tumors of various histotypes indicate the importance of further correlation analysis of Tubb3 expression level with the patients' life span in order to identify the prognostic value of the marker.

Calibrating Observational Health Record Data Against a Randomized Trial

The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this. To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source. This retrospective cohort study used an EHR database spanning from April 2007 to February 2023. Follow-up began on treatment initiation and proceeded until an outcome event, loss to follow-up, end of data, or end of study period (640 days). The population-based cohort was ascertained from EHRs provided by 52 health systems across the US. Eligibility criteria were defined as closely as possible to the benchmark RCT. Patients with non-small cell lung cancer initiating first-line treatment for metastatic disease were included. Patients with evidence of squamous non-small cell lung cancer, primary nonlung malignant neoplasms, or identified EGFR/ALK variations were excluded. Data were analyzed from June to October 2023. Initiation of first-line pembrolizumab and chemotherapy and chemotherapy alone. Chemotherapy in both groups was defined as a combination of pemetrexed and platinum-based (carboplatin or cisplatin) therapy. Outcomes of interest were 12-month survival probability and mortality hazard ratio (HR). A total of 1854 patients (mean [SD] age, 63.7 [9.6] years; 971 [52.4%] men) were eligible, including 589 patients who initiated pembrolizumab and chemotherapy and 1265 patients who initiated chemotherapy only. The cohort included 364 Black patients (19.6%) and 1445 White patients (77.9%). The 12-month survival probabilities were 0.60 (95% CI, 0.54-0.65) in the pembrolizumab group and 0.58 (95% CI, 0.55-0.62) in the chemotherapy-only group, compared with 0.69 (95% CI, 0.64-0.74) in the KEYNOTE-189 pembrolizumab group and 0.49 (95% CI, 0.42-0.56) in the KEYNOTE-189 chemotherapy-only group. The mortality HR was 0.95 (95% CI, 0.78-1.16), compared with 0.49 (95% CI, 0.38-0.64) in the KEYNOTE-189 RCT. In this cohort study piloting an RCT emulation, results were incongruous with the benchmark trial. Differences in patient treatment and data capture between the RCT and EHR populations, confounding by indication, treatment crossover, and accuracy of captured diagnoses may explain these findings. Future feasibility assessments will require data sources to have important oncology-specific measures curated.

Circulating Exosomal miRNA Profiles in Non-Small Cell Lung Cancers.

A growing number of studies have shown that microRNAs (miRNAs) can exert oncogenic or tumor suppressor activities in a variety of cancers, including lung cancer. Given their presence in exosome preparations, microRNA molecules may in fact participate in exosomal intercellular transfers and signaling. In the present study, we examined the profile of 25 circulating exosomal microRNAs in ostensibly healthy controls compared to patients with squamous cell lung cancers (SQCLC) or lung adenocarcinomas (LUAD). Eight miRNAs, namely, miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, and miR-9-5p, were highly enriched in the cohort and selected for further analyses. All miRNAs were readily detected in non-small cell lung cancer (NSCLC) patients of both sexes at all cancer stages, and their levels in exosomes correlated with the clinicopathological characteristics of tumors. Thus, the presence of these miRNAs in circulating exosomes may contribute to the regulation of oncogenic activity in patients with NSCLC.

Metastatic squamous non-small cell lung cancer – complete response following desmocollin-3 targeting immunotherapy as a monotherapy – A case report

Metastatic squamous non-small cell lung cancer – complete response following desmocollin-3 targeting immunotherapy as a monotherapy – A case report

1225P Perioperative serplulimab and chemotherapy in patients with resectable squamous non-small cell lung cancer: An open-label, single-arm, phase II trial

1225P Perioperative serplulimab and chemotherapy in patients with resectable squamous non-small cell lung cancer: An open-label, single-arm, phase II trial

Neutrophil estimation and prognosis analysis based on existing lung squamous cell carcinoma datasets: the development and validation of a prognosis prediction model.

Notwithstanding the rapid developments in precision medicine in recent years, lung cancer still has a low survival rate, especially lung squamous cell cancer (LUSC). The tumor microenvironment (TME) plays an important role in the progression of lung cancer, in which high neutrophil levels are correlated with poor prognosis, potentially due to their interactions with tumor cells via pro-inflammatory cytokines and chemokines. However, the precise mechanisms of how neutrophils influence lung cancer remain unclear. This study aims to explore these mechanisms and develop a prognosis predictive model in LUSC, addressing the knowledge gap in neutrophil-related cancer pathogenesis. LUSC datasets from the Xena Hub and Gene Expression Omnibus (GEO) databases were used, comprising 473 tumor samples and 195 tumor samples, respectively. Neutrophil contents in these samples were estimated using CIBERSORT, xCell, and microenvironment cell populations (MCP) counter tools. Differentially expressed genes (DEGs) were identified using DEseq2, and a weighted gene co-expression network analysis (WGCNA) was performed to identify neutrophil-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression model was constructed for prognosis prediction, and the model's accuracy was validated using Kaplan-Meier survival curves and time-dependent receiver operating characteristic (ROC) curves. Additionally, genomic changes, immune correlations, drug sensitivity, and immunotherapy response were analyzed to further validate the model's predictive power. Neutrophil content was significantly higher in adjacent normal tissue compared to LUSC tissue (P<0.001). High neutrophil content was associated with worse overall survival (OS) (P=0.02), disease-free survival (DFS) (P=0.02), and progression-free survival (PFS) (P=0.03) using different software estimates. Nine gene modules were identified, with blue and yellow modules showing strong correlations with neutrophil prognosis (P<0.001). Eight genes were selected for the prognostic model, which accurately predicted 1-, 3-, and 5-year survival in both the training set [area under the curve (AUC) value =0.60, 0.63, 0.66, respectively] and validation set (AUC value =0.58, 0.58, 0.59, respectively), with significant prognosis differences between high- and low-risk groups (P<0.001). The model's independent prognostic factors included risk group, pathologic M stage, and tumor stage (P<0.05). A further molecular mechanism analysis revealed differences between risk groups were revealed in immune checkpoint and human leukocyte antigen (HLA) gene expression, hallmark pathways, drug sensitivity, and immunotherapy responses. This study established a risk-score model that effectively predicts the prognosis of LUSC patients and sheds light on the molecular mechanisms involved. The findings enhance the understanding of neutrophil-tumor interactions, offering potential targets for personalized treatments. However, further experimental validation and clinical studies are required to confirm these findings and address study limitations, including reliance on public databases and focus on a specific lung cancer subtype.