Advanced Lung Squamous Cell Carcinoma Research Articles

Establishment of a prognostic signature for patients with advanced lung squamous cell carcinoma based on tumor-infiltrating immune cells.

With the advancements in the fields of science, technology, and medical therapy, there is an increasing awareness among the general public regarding tumor-infiltrating immune cells. These immune cells have a close association with the prognosis of clinical patients with lung cancer. The research used a comprehensive analysis and assessed tumor-infiltrating immune cells in advanced lung squamous cell carcinoma (LUSC) using The Cancer Genome Atlas (TCGA) database and the CIBERSORT algorithm. The research examined 22 types of tumor-infiltrating immune cells and observed notable differences in the infiltration patterns of immune cells between normal tissue and advanced LUSC. Univariate Cox regression analyses revealed a positive correlation between macrophages M2 and patient prognoses, as well as potential influences on patient prognosis by natural killer (NK) cells resting, monocytes, and activated mast cells. Multivariate Cox regression models were developed, incorporating three types of immune cells. The efficacy of the model was evaluated using a receiver operating characteristic (ROC) curve. Furthermore, the research constructed a nomogram model to individually predict the mortality risk in patients with advanced LUSC. This prediction model serves as a valuable tool for clinicians, enabling them to provide effective guidance based on tumor-infiltrating immune cells for advanced LUSC patients. The research comprehensively analyzed and evaluated 22 types of tumor-infiltrating immune cells from advanced LUSC, revealing the correlation between immune cell infiltration and overall survival (OS) in clinical patients. Based on the nomogram of NK cells resting, monocytes, and macrophages M2, it can make specific prognostic predictions for advanced LUSC patients.

Pre-treatment plasma-informed circulating tumor DNA detection as an early identification of therapeutic benefit for patients with untreated advanced lung squamous cell carcinoma.

9041 Background: Circulating tumor DNA (ctDNA) detection as a promising prognostic factor to assess treatment response has been widely studied with customized tumor-informed strategies, the application of which was limited by the inaccessibility for tumor biopsies in a substantial proportion of patients. To overcome this challenge, we presented a proof-of-concept study for the development of a novel personalized pre-treatment plasma-informed next generation sequencing (NGS) panel and investigated its prognostic value for first line treatment in patients with advanced lung squamous cell carcinoma (LUSC). Methods: Paired plasma and white blood cell (WBC) samples were collected from 227 of stage IIIB-IV LUSC patients who were treated with first line either chemotherapy or chemotherapy plus PD-1 blockade at pre- and post-treatment. Somatic mutations in pre-treatment plasma were identified with a 769-gene based NGS panel (Genecast, Wuxi, China) followed with germline or clonal hematopoietic variants filtering by referring to the WBC samples. Positive variants detected in the pre-treatment plasma served as a basis for personalized variants tracking in post-treatment plasma. ctDNA kinetics was measured by plasmaDelta (Δgenevaf=((post-treatment genevaf – pre-treatment genevaf) / pre-treatment genevaf; genevaf was defined by variant allele frequency for each individual gene). Progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint were assessed. Results: ctDNA positivity was observed in 80% (182/227) of pre-treatment samples and subsequently 54% (99/182) of post-treatment samples. ctDNA positivity at post-treatment was shown to be a significant predictor for both PFS and OS in the whole group as well in the sub-treatment groups (Table). After adjusting for clinicopathologic variables, ctDNA positivity remained significantly associated with both worse PFS and OS (PFS: HR = 2.3, P <0.001 and OS: HR= 2.56, P <0.001). ctDNA kinetics further identified a worse treatment response group. Patients with high plasmaDelta had remarkably worse outcomes than patients with low plasmaDelta (PFS: HR =4.8; 95%CI=2.8-8.3; P < 0.001 and OS: HR=2.8; 95%CI=1.7-4.6; P <0.001). Conclusions: These results demonstrated the feasibility of pre-treatment plasma-informed ctDNA detection and kinetics for monitoring treatment response in LUSC patients whose tumor biopsies were unavailable. [Table: see text]

Long non-coding RNA DSCAS regulates cisplatin sensitivity in lung squamous cell carcinoma by competitively binding to miR-646-3p

BackgroundPlatinum-based chemotherapy is the main treatment for advanced lung squamous cell carcinoma (LUSC). Eventually, patients with LUSC develop resistance to cisplatin, which affects the prognosis. Hence, the researchers sought to find a lncRNA in LUSC that affects resistance to cisplatin. MethodsThe lncRNA microarray assay was used to screen the differential expression of lncRNA. qPCR was used to detect lncRNA DSCAS (DSCAS) expression in tissues and cell lines. Lentiviral transfection was used to regulate the expression of DSCAS. CCK-8, colony formation, wound healing, transwell, and flow cytometry assays were used to assess the biological behaviors and sensitivity to cisplatin of LUSC cell. RNA-RNA interaction was tested using the dual luciferase reporting assay, RNA-IP, and RNA-RNA pull-down assay. The downstream pathway of DSCAS was verified by qPCR and Western blotting assays. ResultsDSCAS was highly expressed in LUSC tissues and cells, and its expression levels were higher in cisplatin-insensitive tissues than in cisplatin-sensitive tissues. Elevation of DSCAS promoted cell proliferation, migration and invasion as well as increased cisplatin resistance of lung cancer cells, while demotion of DSCAS inhibited cell proliferation, migration and invasion as well as decreased the cisplatin resistance of lung cancer cells. DSCAS bound to miR-646-3p to regulate the expression of Bcl-2 and Survivin, which affected the cell apoptosis and sensitivity to cisplatin in LUSC cells. ConclusionsDSCAS regulates biological behavior and cisplatin sensitivity in LUSC cells by competitively binding to miR-646-3p to mediate the expression of Survivin and Bcl-2, known as apoptosis-related proteins.

Phase 2 clinical trial of the proautophagic drug ABTL0812 combined with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung carcinoma.

9059 Background: ABTL0812 induces the inhibition of Akt/mTOR pathway by upregulation of TRIB3 protein, an endogenous Akt inhibitor, and promotes endoplasmic reticulum (ER) stress. As a result, ABTL0812 induces cytotoxic autophagy that leads to specific death of cancer cells, without affecting non-tumor cell viability. A Phase II clinical trial was designed where ABTL0812 was evaluated in combination with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung cancer (NSCLC). Methods: ABTL0812 was administered 1300 mg TID orally with 175 mg/m2 paclitaxel and AUC5 carboplatin every 3 weeks, for up to 8 cycles, followed by ABTL0812 as a maintenance until disease progression or unacceptable toxicity. The study enrolled patients with non-irradiable IIIb stage or stage IV squamous NSCLC. Primary endpoint was overall response rate (ORR) by RECIST criteria v.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety and tolerability according to CTCAE v4.03, pharmacokinetics (PK) of ABTL0812 enantiomers ((-)-ABTL and (+)-ABTL) and pharmacodynamics assessed by two surrogate blood biomarkers: TRIB3 and CHOP. Results: Forty patients were included; median age was 66.1 years old; 90% men/10% women; 100% ECOG 0-1; 30% current smokers/67.5% former smokers and 37.5% had received prior chemotherapy > 12 months before inclusion. 39 patients had at least 1 adverse event (AE), anemia appeared in 32.5% of the patients (5.0% grade 3), neutropenia in 27.5% (25% grades 3-4) and thrombocytopenia in 17.5% of the patients (2.5% grade 3). For non-hematological AEs, asthenia was reported in 62.5% of the patients (2.5% grade 3); diarrhea in 45% (no grade 3-4) and nausea in 37.5% (5% grades 3-4). Twenty-five patients reach the primary endpoint for efficacy evaluation. ORR was 52.0% (95% CI 34.2-65.9) and 32.0% of the patients had stable disease. Median OS was 22.5 months (10.4-NC), median progression free survival 6.2 months (4.4-8.8), and DOR 5.1 months (3.9-7.4). Area under the curve (µg·h/ml) for (-)-ABTL and (+)-ABTL were 39.0±12.3 and 17.1±6.3 respectively, maximal concentrations (µg/ml) were 6.4±2.6 and 5.1±2.2 and minimum concentrations (µg/ml) 2.2±1.5 and 0.8±1.3. TRIB3 and CHOP PD biomarkers were induced by the treatment. Conclusions: The combination of ABTL0812 with paclitaxel and carboplatin shows survival outcomes that compare favorably with historical controls in squamous-NSCLC with an acceptable safety profile. PK analysis is compatible with drug activity, and pharmacodynamic analysis shows drug engagement. Clinical trial information: NCT03366480 .

Sequential intravenous chemotherapy with drug-eluting bead bronchial arterial chemoembolization for the treatment of stages III and IV lung squamous cell carcinoma: A retrospective controlled clinical study.

8548 Background: To determine the differences in efficacy and safety between drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) combined with intravenous chemotherapy and systemic chemotherapy alone for the treatment of stages III and IV lung squamous cell carcinoma (LSCC). Methods: 136 patients with stages III and IV LSCC were retrospectively recruited between January 2018 and August 2021 and divided into group A (chemotherapy-only, N = 95) and group B (DEB-BACE combined with intravenous chemotherapy, N = 41). The short-term efficacy, hemoptysis and dyspnea remission rates, and incidence of adverse reactions were compared between the two groups. Survival estimation was performed by Kaplan-Meier, and the Log-rank test was performed to compare survival differences between groups. Results: The One-month DCR (90.2% vs. 49.5%) and ORR (75.6% vs. 38.9%) were better in group B than in group A (both P < 0.05). Progression-free survival (PFS) was 8.0 months in Group B and 6.0 months in Group A, a statistically significant difference (P < 0.05). The PFS rates at 6, 12, and 24 months were 63.4%, 24.4%, 0.0%, 43.2%, 13.7%, and 0.0% in groups B and A, respectively, this difference was significant (P < 0.05). The median overall survival was better in group B than in group A (19.0 vs 14.0 months, P < 0.05). The OS rates at 6, 12, and 24 months were 100%, 85.4%, 26.8%, 78.9%, 56.8%, and 22.1% in groups B and A, respectively, with statistically significant differences (P < 0.05). The hemoptysis and dyspnea remission rates were better in group B than in group A within one month after treatment (P < 0.05), however, in terms of the incidence of adverse reactions, incidences, such as post-treatment fatigue and bone marrow suppression, were significantly lower in Group B than in Group A during the follow-up period (P < 0.05). Conclusions: DEB-BACE combined with intravenous chemotherapy is effective for the treatment of advanced LSCC, with lower adverse reactions, and significant improvement in patients' hemoptysis and dyspnea symptoms, which is worthy of clinical application.

Efficacy of radiotherapy in combination with first-line immunotherapy and chemotherapy for advanced lung squamous cell carcinoma: a propensity score analysis.

To compare the efficacy and safety of radiotherapy in combination with immunotherapy after achieving disease control from the first-line combination therapy of platinum-based chemotherapy and immunotherapy for advanced lung squamous cell carcinoma (LUSC). This study retrospectively evaluated the patients with advanced LUSC treated with the combination of radiotherapy with immunotherapy and chemotherapy (ICRT group, n = 52) or immunotherapy and chemotherapy (ICT group, n = 63) as the first-line treatment from April 2018 to April 2022. Using propensity score matching (PSM), 50 pairs were created, while the confounders and bias were controlled. The objective response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed in the two groups. The PFS and OS were re-analyzed separately for patients treated with thoracic radiotherapy. After PSM, the median PFS (12.23 vs. 7.43 months; P <0.001) and median OS (19.7 vs. 12.9 months; P <0.001) were significantly longer in the ICRT group than those in the ICT group. Both the PFS and OS rates were also significantly higher in the ICRT group than those in the ICT group, except for the OS rates in the 6th and 12th months. The mDOR of the ICRT group patients (17.10 vs. 8.27 months; P <0.001) was significantly higher than that of the ICT group patients. The median PFS, median OS, and local control rate were significantly longer in the thoracic radiotherapy group than in the control group. Radiation pneumonia was the most common adverse effect after radiotherapy; however, no treatment-related deaths occurred. The Cox regression analysis showed that ECOG scores 0-1, presence of necrosis in the tumor, radiotherapy, and optimal efficacy better than the stable disease (SD) were independent factors, affecting the PFS, while the patients with recurrent post-operative, pre-treatment NLR, radiotherapy, and optimal efficacy better than SD were the independent factors, affecting the OS. The combination of radiotherapy with systematic immunotherapy and chemotherapy for the advanced LUSC was effective with tolerable adverse effects.

Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy.

Bronchoscopy has been widely used for the therapy of lung cancer. This study aimed to evaluate the therapeutic efficacy and adverse reactions of bronchoscopic intratumoral injection of endostar and cisplatin in patients with lung squamous cell carcinoma (LSCC). A total of 40 LSCC patients who underwent conventional chemoradiotherapy were included in this study, and 20 of them received a bronchoscopic injection of endostar and cisplatin as an additive therapeutic modality (treatment group). The clinical response rate, progression-free survival (PFS), and adverse reactions of the patients were compared and analyzed. The treatment group had better short- and long-term therapeutic efficacy compared to the control group, but no significant differences were observed between the two therapeutic regimens in adverse reactions. Elderly and advanced LSCC patients had worse therapeutic efficacy and a high probability of adverse reactions after the therapy. Collectively, our analysis data demonstrated that the bronchoscopic intratumoral injection of endostar and cisplatin had improved therapeutic efficacy, and the cardiovascular adverse reactions were within the controllable range in the treatment of LSCC in clinical practices.

The critical role of serum thymidine kinase 1(STK1) in predicting prognosis for immunotherapy in T4 stage lung squamous cell carcinoma

PurposeThe role of serum thymidine kinase 1 (STK1) in predicting the prognosis of T4-stage lung squamous cell carcinoma (LUSC) with immunotherapy is the focus of our work. MethodsA total of 180 LUSC patients were enrolled. In this study, according to the T stage, the patients were divided into two groups: the T1-T2 stage and the T3-T4 stage. Receiver operating characteristic (ROC) curves were used to determine the best cutoff value for predicting overall survival (OS) outcomes. The next step is to use this cutoff value to introduce univariate and multivariate Cox regression models to screen the prognostic factors in different T stages of LUSC. The association of STK1 with other clinicopathological factors was also determined. Finally, to further explore the link between STK1 and the staging of LUSC patients, we have further divided the staging into T1-3 and T4 stages. We identified factors influencing the prognosis of patients who received immunotherapy in T4 stage LUSC. ResultsFirst, we determined that the optimal cutoff for STK1 for predicting OS outcome was 1.165 pmol/L. Correlation analysis revealed that STK1 was over-expressed in LUSC patients at the T3-4 stage. Univariate and multivariate analysis showed that immunotherapy was an independent prognostic factor in patients with T4 stage LUSC. In the group of patients who received immunotherapy or not, the STK1 expression level was found to be an independent prognostic factor in T4 LUSC patients receiving PD-1/PD-L1 inhibitor treatment; patients with high levels of STK1 had an increased risk of death (95%CI = 1.028–2.04). ConclusionSTK1 is associated with a higher T stage and may be an effective prognostic marker for advanced LUSC immunotherapy patients.

Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study

PurposeTo analyze the efficacy and safety of bronchial arterial embolization (BACE) with drug-eluting beads (DEB) versus bronchial artery infusion (BAI) followed by polyvinyl alcohol (PVA) particle embolization for the treatment of advanced squamous cell lung cancer after the failure of systemic therapy. MethodThirty-six patients with advanced squamous cell lung cancer who underwent bronchial arterial interventional therapy were included in this retrospective study. The DEB group (n = 20) was treated with nedaplatin and DEB loaded with gemcitabine, and the PVA group (n = 16) BAI with nedaplatin and gemcitabine followed by embolization with PVA particles. The treatment efficacy and complications were analyzed. ResultsThe technical success rate was 100 %. The two groups were followed up for a median period of 8.9 months. The mean overall survival (OS) in the DEB group was 12.6 months (95 % CI:9.99–15.21), which was significantly longer than 8.14 months (95 % CI:6.07–10.2) in the PVA group (p = 0.007). The median progression-free survival (PFS) in the DEB group was 4.3 months (95 % CI:2.33–6.27), significantly longer than 3.2 months (95 % CI:2.55–3.85) in the PVA group (p = 0.030). The objective response rate (ORR) six months after the procedure was 50 % in the DEB group and 12.5 % in the PVA group. In the univariate and multivariate analyses, DEB-BACE was an independent prognostic factor for survival. Only grade 1 adverse events like fever, chest pain, and cough were seen. ConclusionsDEB-BACE may be a good choice for patients with advanced lung squamous cell carcinoma, as it could prolong OS and PFS without increasing adverse events.

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Docetaxel Plus Nedaplatin or Carboplatin as Second-Line Chemotherapy for Advanced Lung Squamous Cell Carcinoma in Real-World Practice: A Single-Center Experience.

Although single-drug chemotherapy regimens were used as second-line chemotherapy for advanced lung squamous cell carcinoma (LSCC) patients, there are still no standard guidelines for second-line chemotherapy. The purpose of this study was to compare the efficacy and safety of docetaxel combined with nedaplatin or carboplatin in the second-line treatment of advanced LSCC patients. One hundred and ninety-six LSCC patients receiving docetaxel plus nedaplatin (DN, n = 96) or carboplatin (DC, n = 100) were retrospectively collected until disease progression or unacceptable toxicity. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed in the two groups. The ORR was 18.8% versus 16.0%, and the DCR was 39.6% versus 34.0% in DN group and DC group (P > .05 and P > .05), respectively. The PFS was 5.3 versus 3.8 months, and the OS was 8.5 and 6.7 months in DN group and DC group (P = .013 and P = .404), respectively. The rate of digestive reaction and hepatotoxicity was similar in DN and DC groups, whereas more patients in DC group than in DN group suffered from leucopenia (P < .05). Docetaxel combined with nedaplatin is an effective regimen for advanced LSCC patients. Compared with a similar regimen with carboplatin, the response rate was similar; however, nedaplatin regimen shows some superiority as regards survival and some treatment side effect.

Abstract PR004: The role of NOTCH1 in bronchial pre-malignant lesions

Abstract Continuous carcinogen exposure through smoking creates a field of injury along the airway and resulting in mutations which promote remodeling of the bronchial epithelium. Over time lesions can form and exhibit increasing abnormalities progressing from goblet cell hyperplasia (GCH) which is the earliest detectable premalignant state through hyperplasia and squamous metaplasia to incremental stages of dysplasia, carcinoma in situ (CIS) and eventually to frank carcinoma. Unfortunately, more than half of all lung cancer patients are diagnosed with metastatic disease with a dismal 5-year survival rate of only 5.2%. However, when diagnosed at an early stage, the 5-year survival rate is more than 10 times as high. Our group has identified NOTCH1 as the most frequently mutated gene in progressive lung premalignant lesions (PMLs). However, these mutations are significantly less common in advanced lung squamous cell carcinoma (LUSC), indicating a role for NOTCH1 in the pre-tumorigenic environment rather than contributing to the actual tumor mass. Transcriptomic profiling of NOTCH1 mutated lesions identified up regulation of peri-goblet cells (PGC), a newly identified bronchial epithelial cell type that is associated with smoking, and a down regulation of immune components. Using highly multiplex Imaging Mass Cytometry (IMC) to analyze the epithelium of NOTCH1 mutated PMLs and its interplay with the immune system in situ. We identified a shift in epithelial composition with an increase in un- and de-differentiated cells. Interestingly, PGC appear to be an intermediate cell type on a previously undescribed path to goblet cell differentiation. In a parallel approach we are modeling NOTCH1 driven dysplasia in vitro to gain insight into the molecular mechanisms of lesion progression. Primary human bronchial epithelial cells (hBECs) grown at the air-liquid interface (ALI) into mature epithelia are exposed to cigarette smoke condensate (CSC) or IL-13 to model the early stages of bronchial airway dysplasia. Continuous exposure of these differentiating cultures to either stimulus increases the abundance of goblet cells and PGCs in a dose dependent manner with IL-13 additionally leading to the loss of baso-apical organization of the epithelium. After successfully modeling the first stage of bronchial epithelial dysplasia we are now advancing our model by co-culturing primary hBECs with NOTCH1 mutated cells and to disentangle the pathway of basal-PGC-goblet cell differentiation. Understanding driving forces in early lesion progression will further our ability to discern progressive lesions from those that regress naturally and facilitate interventions that force lesions into regression. Citation Format: Roxana Michaela Pfefferkorn, Darren Jianjhih Chiu, Divya Lakshmi Venkatraman, Jennifer Ellen Beane, Sarah Anne Mazzilli, Joshua David Campbell. The role of NOTCH1 in bronchial pre-malignant lesions. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr PR004.

免疫联合放疗一线治疗局部晚期肺鳞癌15例临床观察

免疫联合放疗一线治疗局部晚期肺鳞癌15例临床观察

Downregulation of T-cell cytotoxic marker IL18R1 promotes cancer proliferation and migration and is associated with dismal prognosis and immunity in lung squamous cell carcinoma.

Immunotherapy can improve the survival of patients with advanced lung squamous cell carcinoma (LUSC). T cytotoxic cells are one of the main members of the immune microenvironment. Herein, we aimed to identify the roles of T-cell cytotoxic markers interleukin 18 (IL18) receptor 1 (IL18R1) in the LUSC progression using bioinformatics, clinical tissue specimen, and cell experiment. We assessed the association between the IL18R1 expression and immune infiltration and IL18R1-related competing RNA network. The IL18R1 expression was downregulated in the LUSC tissues. The IL18R1 expression downregulation was associated with diagnosis and short overall survival and disease-specific survival, and it was also an independent risk factor for dismal survival time in LUSC. IL18R1-related nomograms predicted the survival time of patients with LUSC. IL18R1 overexpression inhibited the proliferation, migration, and invasion of LUSC cells. The IL18R1 expression was significantly associated with the microenvironment (stromal, immune, and estimate scores), immune cells (such as the T cells, cytotoxic cells, CD8 T cells), and immune cell markers (such as the CD8A, PD-1, and CTLA4) in LUSC. AC091563.1 and RBPMS-AS1 downregulation was positively associated with the IL18R1 expression, negatively associated with the miR-128-3p expression, and associated with short disease-specific survival and progression in LUSC. In conclusion, IL18R1 was significantly downregulated and associated with the prognosis and immune microenvironment. IL18R1 overexpression inhibits the growth and migration of cancer cells in LUSC. Furthermore, AC091563.1 and RBPMS-AS1 might compete with IL18R1 to bind miR-128-3p for participating in LUSC progression. These results showed that IL18R1 is a biomarker for evaluating the prognosis of patients with LUSC.

Efficacy and Safety of the PD-1 Inhibitor Combined with Albumin-Bound Paclitaxel and Nedaplatin in Preoperative Neoadjuvant Therapy of Unresectable Stage III Lung Squamous Cell Carcinoma.

To investigate the efficacy and safety of preoperative neoadjuvant therapy (PD-1 inhibitor plus nab-PTX and nedaplatin) for resectable stage III lung squamous cell carcinoma (SCC) patients. Patients with locally advanced lung SCC (stage IIIA, IIIB) who received PD-1 inhibitor combined with nab-PTX and NED between February 2019 and June 2021 in Weihai Municipal Hospital were included and underwent surgical treatment 4 weeks after 2-4 cycles neoadjuvant therapy. The rate of resection R0, the effective rate, the complete pathological remission rate (pCR) and the rate of major pathological remission (MPR) were observed. A total of 14 initially unresectable male patients with lung SCC were included and received neoadjuvant treatment after evaluation. Nine out of 14 patients (64.3%) experienced treatment-related adverse events (TRAE), among which 8 (57.1%) experienced grade (G) I-II TRAEs including nausea, vomiting, fatigue, constipation, elevated ALT and AST, hyperthyroidism, hypothyroidism, rash, granulocytopenia, and thrombocytopenia, and 1 (7.1%) experienced grade III-V TRAEs (G), including granulocytopenia and atelectasis. Thirteen patients (92.86%) achieved RECIST-assessed partial remission (PR), while 1 patient (7.14%) achieved stable disease (SD) on imaging assessment after neoadjuvant treatment and continued to be progression-free for 26 months. Of the 11 patients who underwent resection, all were alive and recurrence/progression-free. MPR and pCR were observed in 2 (18.18%) and 9 (81.82%), respectively. IHC results exhibited that all NSCLC patients exhibited positive PD-L1 expression (9/14, TPS ≥50% or greater; 5/14, 1% < TPS < 50%). Two were negative for ALK, EGFR, and ros-1, and the rest were not examined for driver oncogene mutation. The neoadjuvant therapy of the PD-1 inhibitor combined with nab-PTX and NED demonstrated remarkable therapeutic efficacy and good safety on stage III lung SCC without increasing the risk of TRAE, mortality and surgery-related complications, or impede surgery feasibility.

Effects of Camrelizumab Combined with First-Line Chemotherapy on Serum SCC, VEGF Levels, and Adverse Reactions in Patients with Advanced Squamous Cell Carcinoma of the Lung.

To study the effects of camrelizumab accompanied by first-line chemotherapy on serum SCC, VEGF levels, and adverse reactions in people undergoing advanced lung squamous cell carcinoma. Data sources of the study subjects were 60 people suffering from advanced squamous cell carcinoma of the lung hospitalized from January 2018 to October 2019. They were assigned to two groups, including the control group and the observation group in a random manner, and each consisted of 30 patients. Those in the observation group received camrelizumab (SHR-1210), and gemcitabine plus cisplatin (GP) chemotherapy were treated in the control group. Finally, according to the results, we compare the data of patients in both groups so as to find out the similarities and differences. Among them, the effective efficiency of clinical treatment in the control group reached 36.67%, and that in the observation group reached 56.67%. Intuitively, it can be concluded that the control group showed lower results than the observed group. The observed group turned out to have higher periodic survival and progression free survival (PFS) of patients than the other group. During and after the cycle treatment, the data of SCC and VEGF were reduced to some extent, but the control group appeared to have a more evident reduction rate than the other group. SHR-1210 combined with chemotherapy has a considerable effect in practical application and has excellent clinical performance.

Necitumumab plus gemcitabine and cisplatin in previously treated lung squamous cell carcinoma.

The efficacy and safety of the anti-EGFR antibody necitumumab combined with gemcitabine and cisplatin (N + GC) in the first-line treatment of advanced lung squamous cell carcinoma (LSCC) have been proven. However, the efficacy and safety of N + GC in the second line or later treatment remain unclear. Eleven patients who received N + GC for advanced-stage or recurrent LSCC were enrolled. We retrospectively assessed the patients' clinical characteristics and efficacy and safety of treatment. The median patient age was 73 years (range, 63-77 years). The cohort included nine(81.8%) men and two(18.2%) women. Two (18.2%) patients had postoperative recurrence, and one (9.1%), three (27.3%), one (9.1%), and four (36.4%) patients were diagnosed with stage IIIA, IIIB, IVA, and IVB disease, respectively. Concerning the best overall response, partial response was achieved in five (45.5%) patients, four (36.4%) patients displayed stable disease, and two (18.2%) patients were not evaluable. Median progression-free survival was 6.8 months (range, 1.4-10.3 months). The grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in six (54.5%), three (27.3%), and two (18.2%) patients, respectively. Additionally, grade 3 skin reaction, rash, lung infection, duodenal ulcer, and febrile neutropenia were observed in one (9.1%) patient each. Two (18.2%) patients required treatment interruption because of adverse events. N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential.

Determination of EGFR Mutation Prevalence in Advanced and Metastatic Lung Squamous Cell Carcinoma in Vietnam

Abstract: This paper aims to determine the rate of epidermal growth factor receptor (EGFR) gene mutations in advanced and metastatic squamous cell lung cancer in Vietnamese patients. EGFR mutation testing was performed on 559 formalin-fixed paraffin-embedded tissue samples from advanced and metastatic squamous cell lung cancer patients by real-time PCR. The results showed that EGFR mutations were found in 8.4%. Most of them were exon 19 deletions, approximately 51.1%. Multivariate analysis showed that EGFR mutations were more prevalent in gender (p&lt;0.0001). In conclusion, EGFR mutation testing should be performed in patients with squamous cell lung cancer.&#x0D; Keywords: Lung squamous cell carcinoma, EGFR gene. &#x0D; &#x0D;

Bronchial artery chemoembolization with apatinib for treatment of central lung squamous cell carcinoma.

To evaluation the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with apatinib for treatment of advanced central lung squamous cell carcinoma (LSCC). Forty-seven patients with pathologically diagnosed stage IIIB or IV central LSCC that was not resectable were selected among hospital patients presenting after November 2016. Twenty-one patients were treated with BACE combined with apatinib; the remaining patients served as a control group treated with BACE alone. Objective response rate (ORR) and disease control rate (DCR) were evaluated with postoperative contrast-enhanced CT scans at 3, 6, and 12 months. Progression-free survival (PFS) curves were used to evaluate curative effects. Adverse events were recorded to assess safety. BACE operations were successfully completed in all 47 patients. Significant differences were found at six and 12 months (P < 0.05). Median PFS was 322 days in the observation group and 209 days in the control group: a statistically significant difference (P = 0.042). One-year survival rates were 76.19% and 46.15% for observation and control patients, respectively; this difference was also significant (P = 0.037). Three patients in the observation group received emergency interventional embolization for hemoptysis, and patients with grade III or greater adverse reaction events (AE) accounted for 19.05% of patients (4/21); these subjects improved or were controlled after active treatment. BACE combined with apatinib is effective for treatment of advanced central LSCC, with definite short-term efficacy, controllable risk, and high safety. Investigation with a larger sample size is warranted to confirm study results.

EP02.04-010 Clinical Outcomes After Neoadjuvant Tislelizumab plus Chemotherapy in Resectable Stage IIIA-B NSCLC: A Retrospective Study

Tislelizumab combined with chemotherapy was approved for first-line treatment of advanced squamous cell lung carcinoma and non-squamous non-small cell lung carcinoma in China. This study aimed to evaluate the efficacy of neoadjuvant Tislelizumab plus chemotherapy in resectable stage IIIA-B NSCLC in a real-world setting.