Abstract 2514: Cell-free chromatin particles released into the microenvironment from dying tumor cells activate cancer hallmarks in surviving cells: a study in advanced squamous cell carcinoma of oral cavity with therapeutic implications

2021 ◽  
Author(s):  
Indraneel Mittra ◽  
Hitesh Singhavi ◽  
Aishwarya Pilankar ◽  
Venkat Raghuram Gorantla ◽  
Sophiya Siddiqui ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Advanced Squamous Cell Carcinoma ◽  
Therapeutic Implications ◽  
Cancer Hallmarks

PD-L1 and survival in oral cavity squamous cell carcinoma

2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Immune Cells ◽  
Negative Impact ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Effect Of Pd

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

The KRAS mutation status and resistance to cetuximab in patients with squamous cell carcinoma of oral cavity.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15514-e15514
Author(s):  
Aza A. Lyanova ◽  
Liubov Yu Vladimirova ◽  
Marina A. Engibaryan ◽  
Natalia A. Abramova ◽  
Irina L. Popova ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Clonal Evolution ◽  
Response To Therapy ◽  
Control Group ◽  
Mutant Type ◽  
Droplet Pcr

e15514 Background: The standard treatment of squamous cell carcinoma of the tongue and the mucosa of the bottom of the oral cavity (SCCTOM) is chemotherapy (CT) in combination with cetuximab (mC, anti-EGFR antibody). However, not all patients manage to achieve positive results. A common cause of resistance to anti-EGFR antibodies is the constitutive activation of mediators of the underlying signaling pathways. Therefore, the aim of the study was to analyze mutations in the KRAS using the Digital Droplet PCR method in patients with SCCTOM on the background of CT in combination with targeted therapy or standard CT. Methods: The study used the QX200 system (Bio-Rad) and the ddPCRtm KRAS Screening Multiplex Kit (7 mutations). The study included 60 patients with T3-4N0-1M0 SCCTOM. The main group consisted of 30 patients (cisplatin, 5-fluorouracil+cetuximab). The control group consisted of 30 patients (CT). For research, cfDNA from blood plasma was used. Analysis of the data was performed using QuantaSoft v1.7.4. Results: The frequency of the KRAS mutant type (mtKRAS) is 43% before treatment and 32% after treatment (n = 60). In the group of patients CT+mC the incidence of mtKRAS before treatment was 40%, after treatment - 20%. In the group of patients CT without mC the incidence of mtKRAS before treatment was 47%, after treatment - 43%. Decrease of 20% (p = 0.00089) in the frequency of mtKRAS after CT+mC was found, while it was 23% (p = 0.00009) lower than the frequency of mtKRAS after CT without mC. After treatment, in the CT+mC group of patients, the number of mtKRAS DNA copies increased 1.5 times (p = 0.048). Analysis of clinical response to therapy allowed us to divide the main and control groups of patients into 2: sensitive and resistant to therapy. After treatment, a change in the mtKRAS ratio was not found in the subgroup sensitive to mC compared with the period before treatment, while the frequency of mtKRAS was reduced by 3 times (p = 0.009). In the mC-resistant subgroup, the mtKRAS ratio increased 1.9 times compared to the period before treatment (p = 0.009), while the frequency of mtKRAS increased 3.5 times compared with the mC-sensitive group (p = 0.0045). Conclusions: Prior to treatment, patients resistant to CT+mC were characterized by an increased occurrence of mutations in the KRAS and an apparently large number of tumor cells carrying mutations. The use of mCs caused a change in the direction of the clonal evolution of tumor cells - leading to an increase in the number of cells carrying mtKRAS (conditions were created for the elimination of cells with mutation in EGFR and KRAS wild type).

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