Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function

Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (n = 8, FDR < 0.05; n = 55, raw p-values < 0.05), after XL-147 treatment (n = 4, FDR < 0.05; n = 26, raw p-values < 0.05) and after Budesonide treatment (n = 1, FDR < 0.05; n = 36, raw p-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer.

Download Full-text

Abstract 142: Mutation and immune profiles in early-stage lung squamous cell carcinoma

10.1158/1538-7445.am2016-142 ◽

2016 ◽

Cited By ~ 1

Author(s):

Murim Choi ◽

Humam Kadara ◽

Jiexin Zhang ◽

Edwin Parra Cuentas ◽

Jaime Rodriguez Canales ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Lung Squamous Cell Carcinoma

Download Full-text

Clinical implications of monitoring circulating tumor DNA in early- and late-stage non-small cell lung cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20607 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20607-e20607

Author(s):

Muyun Peng ◽

Lihan Chin ◽

Qi Huang ◽

Wei Yin ◽

Sichuang Tan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Somatic Mutations ◽

Residual Disease ◽

Lung Squamous Cell Carcinoma ◽

Circulating Tumor Dna ◽

Small Cell Lung ◽

Tumor Dna

e20607 Background: Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the most common types of NSCLC are squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The development of noninvasive methods to monitor circulating tumor DNA (ctDNA) continues to be a major challenge in NSCLC. Methods: We investigated if detection of ctDNA after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management.In this cohort study, high-throughput 168 target-gene capture technology and high-sensitivity circulating single molecule amplification and re-sequencing technology (cSMART) were used to detect the somatic mutations in tissues and plasma of patients with NSCLC, respectively. Moreover, ctDNA somatic mutations were used to monitor changes in minimal residual disease during a follow-up period. Results: A total of 169 patients with lung squamous cell carcinoma and adenocarcinoma were included. Detectable levels of ctDNA were present in 60.7% of patients with stage I and 68.8% of patients with late-stage. In patients not treated with adjuvant chemotherapy, ctDNA was detected preoperatively in 46 of 81 (56.8%) patients, 14 (30.4%) of whom had recurred at follow-up of 44 months; recurrence occurred in only 2 (5.7 %) of 35 patients with negative ctDNA. Serial ctDNA status changed from positive to negative during the initial phase of post operation in four patients. Then, ctDNA became positive again after 2 weeks to 3 months, all the four patients with relapse during the follow-up of 44 months. Conclusions: Detection of ctDNA supplies evidence of residual disease and identifies patients at risk of relapse. These observations have implications for the intervention of lung squamous cell carcinoma and adenocarcinoma patients.

Download Full-text

Early stage squamous cell carcinoma of the lower lip: predictive factors for recurrence

The Journal of Laryngology & Otology ◽

10.1017/s0022215116000311 ◽

2016 ◽

Vol 130 (4) ◽

pp. 369-372 ◽

Cited By ~ 6

Author(s):

Y Ozkul ◽

M Songu ◽

A Imre ◽

E Tunc ◽

Z Ozkul ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Local Recurrence ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Clinicopathological Parameters ◽

Lower Lip ◽

Neck Metastasis ◽

Tumour Thickness

AbstractObjective:This study aimed to evaluate the effect of tumour thickness on other clinicopathological parameters in early stage lower lip squamous cell carcinoma.Methods:Forty-six consecutive patients with lower lip squamous cell carcinoma were included in the study. Demographic, clinical and pathological data were retrospectively collected.Results:The mean follow-up period for all patients was 32.0 ± 18.9 months. Forty-four tumours were staged as T1 and two were T2. Twelve patients underwent neck dissection. Two patients presented with neck metastasis in the follow-up period. Four patients (8.7 per cent) had local recurrence. Correlation analysis revealed a significant relationship between microscopic tumour thickness and local tumour recurrence (r = 0.328, p = 0.045).Conclusion:Surgical margin control is important to prevent local recurrence, especially in thicker tumours. In addition, neck metastasis is rare in early stage lower lip squamous cell carcinoma. A ‘wait and see’ policy might be preferred in early stage T1 lower lip squamous cell carcinoma cases.

Download Full-text

Transoral laryngeal microsurgery for early-stage laryngeal basaloid squamous cell carcinoma

BMJ Case Reports ◽

10.1136/bcr-2021-245746 ◽

2021 ◽

Vol 14 (12) ◽

pp. e245746

Author(s):

Barbara Verro ◽

Carmelo Saraniti

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Basaloid Squamous Cell Carcinoma ◽

Neck Node ◽

History Of ◽

Node Metastases ◽

Basaloid Squamous

A 71-year-old man presented to our otolaryngology clinic with dysphagia and dyspnoea. He had a history of smoking for 40 years. Laryngoscopy showed an exophytic, round mass on the left aryepiglottic fold that was entirely excised by transoral laser CO2 microsurgery. Histological assessment revealed a pT1 basaloid squamous cell carcinoma (BSCC) with free-margin resection. He underwent close follow-up and after 3-year follow-up, the patient was free from disease. Laryngeal BSCC is a rare cancer with poor prognosis due to its late diagnosis and early neck node metastases. We report a rare case of early tumour treated by endoscopic surgery without complications or recurrence of disease. However, knowing this type of cancer and making a correct differential diagnosis are important to guarantee the best therapy and prognosis.

Download Full-text

Two-year follow-up of single PD-1 blockade in neoadjuvant resectable NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8522 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8522-8522

Author(s):

Shugeng Gao ◽

Ning Li ◽

Shunyu Gao ◽

Qi Xue ◽

Shuhang Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Disease Free Survival ◽

Postoperative Treatment ◽

R0 Resection ◽

Free Survival ◽

Treatment Naïve

8522 Background: Early stage non-small-cell lung cancer (NSCLC) could benefit from anti-programmed cell death-1 (PD-1) monotherapy; however, the survival profiles remain to be disclosed. Here, we presented the two-year follow-up outcomes from a phase 1b study of sintilimab, an anti-PD-1 inhibitor in the neoadjuvant setting of NSCLC. Methods: Treatment-naive pts with resectable NSCLC (stage IA–IIIB) received two cycles of sintilimab followed by surgical resection. Postoperative treatment of sintilimab was at the discretion of investigator. The primary endpoint was AE, and key secondary endpoints included major pathological response (MPR), disease free survival (DFS) rate of 1 year and 2 years, and overall survival (OS) rate of 2 years. Results: Among 40 enrolled pts, 36 (90%) underwent R0 resection and were included in the R0 resection population. By data cutoff (January 20, 2021), the median follow-up for DFS and OS for all the enrolled pts was 23.9 (IQR 20.5–24.4) months and 26.4 (IQR 24.2–29.0) months. A total of 12 (33.3%) pts experienced relapse, and 6 pts died. The 1-yr and 2-yr DFS rate was 91.7%/73.3%. The 2-yr OS rate for overall population and R0 population was 87.5%/91.7%, respectively. In the R0 resection population, the median DFS and OS were both not reached. Superior 2-year DFS rates were observed in pts who achieved MPR (MPR vs. Non-MPR: 86.7% vs. 63.8%). DFS of pts with non-squamous cell carcinoma tended to be shorter than that of pts with squamous cell carcinoma (HR 2.71 [95%CI 0.67–11.0], p=0.1479). Pts with tumor mutation burden (TMB) ≥10 mutations/Mb and PD-L1 tumor proportion score (TPS)≥50% tended to have a better 2-yr DFS rate compared to those with TMB<10 and TPS<50. [table] For the post-hoc event free survival (EFS) analysis, the same trend was observed with DFS among different subgroups, and patients with TMB ≥10 mutations/Mb had a significant improved EFS (HR 0.125[95% CI 0.02,1.03], P=0.0222). Conclusions: Anti-PD-1 monotherapy emerged to be a promising neoadjuvant therapeutic strategy for resectable NSCLC with improved clinical outcomes. MPR could serve as a surrogate efficacy biomarker in this setting. Clinical trial information: ChiCTR-OIC-17013726. [Table: see text]

Download Full-text