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 ◽  
...  

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.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17528-e17528
Author(s):  
Takeharu Ono ◽  
Koichi Azuma ◽  
Akihiko Kawahara ◽  
Tetsuro Sasada ◽  
Satoshi Hattori ◽  
...  

e17528 Background: Little information has been available regarding immune-related prognostic factors in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). Expression of programmed cell death-ligand 1 (PD-L1) in tumor cells is known to be a mechanism whereby cancer can escape immune surveillance. We investigated the predictive relevance of PD-L1 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density in patients with locally advanced HPSCC receiving neoadjuvant chemotherapy (NAC). Methods: We retrospectively reviewed 83 consecutive patients with advanced HPSCC who had received NAC. PD-L1 expression and TIL density were evaluated by immunohistochemical analysis. Results: Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression free survival (PFS) and overall survival (OS), whereas PD-L1 expression was not correlated with PFS or OS. Subgroup analysis defined by PD-L1 expression in combination with CD8+ TIL density revealed that the PD-L1-/CD8high group showed the longest survival (median PFS and OS were not reached), whereas the PD-L1+/CD8low group showed the shortest PFS (median 7.9 months, p = 0.006) and OS (14.3 months, p = 0.011) by Kaplan-Meier curves. Conclusions: Although there was no significant correlation between PD-L1 expression and prognosis in stage III and IV HPSCC patients who received NAC, the subgroup analysis indicated that combination of lack of PD-L1 expression and higher CD8+ TIL density was significantly associated with favorable survival in these patients. These results suggested that PD-L1 expression levels in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III and IV HPSCC.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e18025-e18025
Author(s):  
Georgy M. Manikhas ◽  
Svetlana I. Kutukova ◽  
Natalia P. Beliak ◽  
Julia V. Ivaskova ◽  
Natalia V. Popova

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 ◽  
...  

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).


2017 ◽  
Vol 28 ◽  
pp. v380
Author(s):  
S. Kutukova ◽  
N. Beliak ◽  
G. Manikhas ◽  
G. Raskin ◽  
Y. Ivaskova ◽  
...  

2019 ◽  
Author(s):  
Jolanta Szelachowska ◽  
Piotr Donizy ◽  
Katarzyna Ratajczak‑Wielgomas ◽  
Agnieszka Halon ◽  
Dominika Zielecka‑Debska ◽  
...  

2015 ◽  
Vol 58 (2) ◽  
pp. 62-65 ◽  
Author(s):  
Petr Čelakovský ◽  
David Kalfeřt ◽  
Katarína Smatanová ◽  
Viktor Chrobok ◽  
Jan Laco

Background: The goal of this prospective study was to determine the frequency of micrometastases in patients with squamous cell carcinoma (SCC) of the oral cavity, pharynx and larynx in whom elective neck dissection was indicated (cN0). Patients and Methods: A total of 12 patients (10 males and 2 females) were enrolled in the study. The age ranged 42–73 years (median 62 years). Elective neck dissection was performed in all patients (8 ipsilateral, 4 bilateral) and a total of 256 lymph nodes were removed and sent for microscopic examination. Results: The presence of tumor cells in cervical lymph nodes was found in 5/12 (42%) patients. Micrometastases of SCC were found in two patients and isolated tumor cells (ITC) in two other patients. In the remaining one patient with oropharyngeal SCC, a micrometastasis of papillary thyroid carcinoma (PTC) was detected. Positive lymph nodes were localized in level II in three patients with SCC of larynx, hypopharynx and tongue base, respectively, in level I in one patient with SCC of oral tongue and in level III in one patient with PTC. Conclusion: Our results indicate that SCC of head and neck has a high potential for creating micrometastases which frequency is higher compared to clinically detected macrometastases. Therefore, elective neck dissection or radiotherapy of the neck should be considered in patients with high risk of occult metastases or micrometastases.


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