Hirna H. Immunocorrection of complications of special methods of treatment of patients with cancer of the oral cavity and oropharynx.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001438

Applicant for

Specialization

  • 221 - Стоматологія

05-01-2023

Specialized Academic Board

ДФ 20.601.038

Ivano-Frankivsk national medical university

Essay

During the completion of the dissertation, 105 patients (92 men and 33 women) with squamous cell cancer of the oral cavity and oropharynx were examined and performed a special treatment. For a comparative analysis, all patients at the phase I of special treatment were randomized into the following groups: I (RT-IT) group – 25 patients who were performed radiation therapy and immunotherapy with alpha/beta defensins (40 mg); II (Ch/RT-IT) group – 20 patients who were performed radiation therapy with regional intra-arterial chemotherapeutic potentiation and immunotherapy (40 mg); III (RT-2IT) group – 20 patients receiving gamma therapy against the background of immunotherapy in an increased dose (60 mg); IV (RT) group – 20 patients receiving only radiation treatment; V (Ch/RT) group – 20 patients who were treated with radiation therapy and regional intra-arterial chemotherapy without immunotherapy. Groups IV and V are comparison groups. The occurrence of a certain degree of epitheliitis was also analyzed according to the relative risk (HR) index. The following results were obtained: a greater risk of epitheliitis of the I, II and III degrees in groups IV and V compared with groups I, II, III, HR=4-5 times for the I degree, HR=3-5 times for the II degree and HR=10-30 times for the III degree of epitheliitis. The data on the effect of the immune agent alpha/beta defensins on systemic antitumour immunity (CD3+ T-cells, natural killer (NK-cell), natural killer T-lymphocytes (T-cell/NK-cell) in patients with cancer of the oral cavity and oropharynx during the performance of radiotherapy and chemotherapy, were padded. Also, for the first time, the mechanism of preservation of the cellular cytotoxic immune response during the treatment of patients with cancer of the oral cavity and oropharynx was studied, which is reflected in the improvement of the treatment tolerability. For the first time, the influence of the immune agent alpha/beta defensins on humoral immunity (IgG, IgM, IgA) of patients with cancer of the oral cavity and oropharynx during radiation and chemoradiation treatment was determined. The effect of the immune agent alpha/beta defensins on mucosal immunological profile (INF-α, INF-γ, IL-6, sIgA) of patients with cancer of the oral cavity and oropharynx during radiation and chemoradiation treatment was studied. The factor characteristics affecting the risk of developing epitheliitis of the III degree, have been determined. The relationship between the components of local and systemic immunity and clinical manifestations of complications of special treatment of patients with cancer of the oral cavity and oropharynx was studied more deeply. The expediency of correcting the complications of radiation or chemoradiation treatment of patients with cancer of the oral cavity and oropharynx with the immunotropic agent alpha/beta defensins is substantiated in order to improve the quality of life, general condition and immediate results of treatment. The results of a complex study made it possible to draw up an algorithm for the safe and effective use of the immunotherapeutic medicine of alpha/beta defensins in patients with cancer of the oral cavity and oropharynx, as a medicine accompanying radiation or chemoradiation therapy to reduce the degree of epitheliitis of the mucous membrane of the oral cavity and oropharynx and other radiation-induced complications. Using this algorithm in clinical practice, the patient’s quality of life and general condition improve after treatment. The possibility of using sIgA as a biomarker of the risk of developing severe epitheliitis in patients with cancer of the oral cavity and oropharynx during special treatment was determined. Based on the laboratory data, recommendations were made for the use of the immunotherapeutic medicine of alpha/beta defensins as an adjuvant to radiation therapy, which enhances its effect through the immunomodulating effect on the antitumour link of immunity in patients with cancer of the oral cavity and oropharynx. The results of the study of the humoral condition of the immune system in patients with cancer of the oral cavity and oropharynx can be used as predictive risk factors for the development of a more severe degree of epitheliitis. Also, their definition in practice allows us to correctly choose the scheme of immunotherapy in order to strengthen the immune resistance of patients. Key words: cancer, oral cavity, oropharynx, antitumor therapy, radiation therapy, chemotherapy, immunotherapy, complications, alpha/beta defensins, radiation epitheliitis, dysphagia, quality of life, oral fluid, secretory immunoglobulin A. Branch-Medicine.

Research papers

1. Гірна ГА, Костишин ІД, Рожко ММ, Лукач ЕВ, Андріїв АВ. Значення імунотерапії препаратом альфа-/бета-дефензинів у розвитку епітеліїту хворих на орофарингеальний рак. Клінічна онкологія. 2021;11(3-4 (43-44)):1-6. DOI: 10.32471/clinicaloncology.2663-466X.43-3.28502

2. Гірна ГА, Костишин ІД, Рожко ММ, Костишин АБ, Міклашевська ОА. Вивчення протипухлинного ефекту імунопрепарату Пропес у хворих на рак порожнини рота і ротоглотки. Вісник проблем біології та медицини. 2021;2(160):287-94. DOI:10.29254/2077-4214-2021-2-160-287-294.

3. Hirna HA, Maltsev DV, Natrus LV, Rozhko MM, Kostyshyn ID, Tanasiychuk IS. Study of the immunomodulating influence of preparation alpha/beta-defensins on chemo/radiotherapy of patients with oral and oropharyngeal cancer. Fiziologichnyi Zhurnal. 2021;67(4):86-96. DOI: https://doi.org/10.15407/fz67.04.086

4. Hirna HA. Analysis of the results of radiotherapy and chemoradiotherapy on the background of immunotherapy of patients with cancer of the oral cavity and oropharynx. Klin Onkol. 2022;35(3):222–31. DOI:10.48095/ccko2022222.

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