Introduction. Lymphomas are a heterogenic group of tumors of the lymphatic and hematopoietic systems, and in many cases tumor process develops in the area of the head and neck including skin and mucosa, orbit, nasal cavity and paranasal sinuses, oral cavity, oropharynx, salivary glands, thyroid, and cervical lymph nodes. Differential diagnosis of lymphomas of the head and neck is complicated because it can be accompanied by another non-tumor pathology. High heterogeneity of lymphomas of the head and neck requires structurization of knowledge on their epidemiological and clinical manifestations.

The study objective is to optimize early diagnosis as it allows to significantly increase cancer alertness in local practitioners, oncologists, diagnosis specialists and, in turn, to decrease verification frequency in generalized disease processes. Study of clinical characteristics of lymphoproliferative disorders of the head and neck leads to increased quality of differential diagnosis.

Materials and methods. A study of lymphoproliferative disorders affecting head and neck was performed. Study material consisted of data on 174 patients hospitalized at the N.N. Blokhin National medical Research Center of Oncology between 1999 and 2020.

Results. Based on the current clinical and morphological classification of lymphoproliferative disorders, data on location of lesions, characteristic signs of extranodal lesions and cervical lymph nodes involvement, as well as methods of diagnosis of lymphomas of the head and neck, are presented.

Conclusion. The obtained data helps solve problems of diagnosis of lymphoproliferative disorders affecting the head and neck and serve as a basis for successful, predictable treatment of lymphomas.

Introduction. Surgery with adjuvant radiation is the standard for treatment of advanced oral and oropharyngeal cancer. with the absence of randomized trials the assessment of the role of postoperative radiotherapy is difficult. Such assessments are usually based on retrospective analyses, whereas patient and tumor status during the time period between the operation and planned start of radiotherapy is not addressed.

The study objective is to assess the role of adjuvant radiotherapy in the treatment of stage III—IV oral and oropharyngeal cancer not associated with human papillomavirus with regard to rapid clinical disease progression after upfront surgical treatment.

Materials and methods. The case histories and outpatient records of 260 patients with oral and oropharyngeal cancer of stage III—IV, not associated with human papillomavirus, from 30 to 82 years old (average age - 56.52 years), operated in 2009-2018, were analyzed. Two groups of patients were identified. group 1 included 152 patients (58 %) irradiated postoperatively and group 2 consisted of 108 patients (42 %) treated surgically only. 22 patients of group 2 experienced rapid clinical disease progression, were deemed unsuitable for adjuvant treatment and formed group 2a. Comparison of the Kaplan-Meier overall survival and locoregional control was made for group 1 and the entire group 2 (formal analysis) and after exclusion from the latter patients of group 2a, based on the hypothesis of inability of radiotherapy to improve oncologic results in patients with such an unfavorable disease course.

Results. Mean follow up was 33.2 months (range 2-121 months). Locoregional control and 5 year overall survival were statistically higher in group 1: 70.4 % versus 45.4 % (р = 0.000) and 40.2 % versus 24.9 % (р = 0.000) that may imply a significant advantage of the combined over monomodal approach. After exclusion of group 2a patients from the analysis both differences considerably narrowed and were 70.4 % versus 55.8 % for locoregional control, 40.2 % versus 31.3 % for overall survival and became statistically insignificant (p = 0.067 and 0.111, respectively).

Conclusion. Rapid clinical disease progression in the time frame between surgical treatment and adjuvant radiotherapy is not a rare phenomenon with a very poor prognosis. It can be one of the reasons for postoperative treatment refusal. formal retrospective analyses of the role of adjuvant treatment without considering causes for its refusal may lead to the overestimation of the combined approach effectiveness.

Introduction. Treatment of the oral cavity is an important problem of current oncology due to high morbidity and mortality reaching 43 % in 5-year period after diagnosis. frequency of positive resection margins is 30 % of cases which partially explains unsatisfactory results of therapy of this pathology and promotes investigation of methods increasing radicalness of surgical treatment of the primary lesion.

The study objective is to evaluate the effectiveness of fluorescent visualization with 5-aminolevulinic acid for assessment of radicalness of surgical intervention in cancer of the oral mucosa.

Materials and methods. In the study, evaluation of the effectiveness of 5-aminolevulinic acid for intraoperative determination of margins of squamous cell carcinoma of the oral mucosa (n = 36) was performed.

Results. Comparison of intraoperative results using 5-aminolevulinic acid and results of histological examination showed that the difference in mean distances from the tumor edge to resection margin was 0.07 mm (95 % confidence interval 2.2905-2.4334) and wasn't statistically significant (p = 0.9519). Sensitivity of intraoperative fluorescent visualization with 5-aminolevulinic acid in diagnosis of resection margins was 100 %, specificity was 92.3 %, accuracy was 92.9 %, effectiveness was 96.1 %. Optimal effect of the fluorescent technique was achieved in patients with exophytic and mixed types of tumor growth without previous treatment.

Conclusion. Method of intraoperative fluorescent visualization with 5-aminolevulinic acid showed high effectiveness (96.1 %) and can be recommended for intraoperative assessment of tumor margins and increase of radicalness of surgical treatment of cancer of the oral mucosa.

Introduction. Surgical treatment of malignant tumors of maxilla and midface results to a combined defects of the soft tissues of the face (upper lip, buccal, zygomatic regions), upper jaw, hard and soft palate, retromolar region, orbit, nasoethmoidal complex. This is one of the most difficult localizations in terms of both the possibility of performing radical surgery and reconstruction. The purpose of reconstruction is not only the elimination of cosmetic deformity, but also the restoration of such vital functions as breathing, swallowing, speech and binocular vision. Till that time, no algorithm has been developed for choosing a method for the reconstruction and there is no comparative analysis of the available methods.

The study objective is to improve the functional and aesthetic results of treatment patients with malignant tumors of the upper jaw and midface.

Materials and methods. For the period from 2014 to 2020 in the Department of Head and Neck Tumors of the N.N. Blokhin National Medical Research Center of Oncology, ministry of Health of Russia microsurgical reconstruction after resections of the upper jaw and midface was performed in 80 patients. most often (25 (31 %) patients) the primary tumor was localized in the maxillary sinus, then hard palate (16 (20 %) patients), soft palate (11 (14 %) patients), retromolar trigone (13 (16 %) patients). primary location at alveolar process of the upper jaw was in 3 (3 %) cases, nasal cavity and cells of the ethmoid labyrinth - in 4 (5 %), frontal sinus - in 5 (6 %), the skin of the cheek and lower eyelid - in 3 (3 %) patients. we defined 4 main types of resection. Type I - combined lower resections of the maxilla and mucosa of the retromolar region, soft palate, lateral wall of the oropharynx (47 (60 %) patients). Type II - total radical maxillectomy (resection of all walls of the upper jaw, including orbital wall) (12 (15 %) patients). In 5 (42 %) cases, the resection was combined and included, in addition to the upper jaw, the skin of the buccal and zygomatic regions. Type III - combined partial resections of the upper jaw (13 (17 %) cases). In 9 (69 %) cases, the block of tissues to be removed included a fragment of the skin of the buccal region, part of the external nose, and lower eyelid. Type Iv - orbitomaxillary resection with orbital exenteration (6 (8 %) patients), including exenteration of the orbit, cells of the ethmoid labyrinth, resection of the frontal bone, medial wall of the orbit, a fragment of the dura mater (4 (67 %) cases), skin of frontal, buccal, zygomatic areas, upper and lower eyelids. for reconstruction of defects in 80 patients we used 82 free flaps. In 76 (93 %) cases, simultaneous resections of the primary lesion and reconstructions were performed, in 6 (7 %) cases, delayed reconstruction after previously performed combined or complex treatment were performed.

Results. In type I resection with limited defects excellent functional and aesthetic results were obtained in all cases of using a radialis fasciocutaneous free flap. In case of subtotal and total defects of the hard palate and the alveolar margin of the upper jaw, the best aesthetic (excellent in 5-46 % of patients, satisfactory in 3-27 %) and functional (excellent speech quality in 8 patients) results were obtained with use free scapula tip flap. In type II resections excellent aesthetic results were obtained in 6 (55 %) patients. In all cases, a chimeric free flap consists of tip of the scapula, fragment of serratus muscle and skin of parascapular region was used. In type III resections in patients with limited defects, 5 (71 %) had excellent aesthetic results, and 2 (29 %) had satisfactory aesthetic results. In all cases a radial free flap was used. In case of half defects of the upper jaw anterior-lateral thigh flap and thoracodorsal free flap was used. In all cases satisfactory aesthetic result was obtained. In type IV resections satisfactory aesthetic results were obtained in all patients.

Conclusion. Preoperative computer 3D modeling is necessary in planning of reconstruction. This allows to determining the type and volume of the defect, plan optimal method of reconstruction, model the required flap geometry, making a template for harvesting flap, calculating the position and number of titanium plates for fixation, and, if necessary, print an individual mesh of the infraorbital wall.

Introduction. Probability of development of multiple primary tumors in patients who received treatment due to head and neck cancers varies between 5.6 and 35.9 % per different sources. moreover, treatment capabilities are severely limited by postoperative anatomical changes and previous radiation therapy, and the second tumor frequently causes death in these patients.

The study objective is to identify the epidemiological features of the development of synchronous and metachronous primary multiple tumors in the head and neck.

Materials and methods. The article analyzes data on 103 patients with multiple primary tumors who received treatment due to tumors of the head and neck between 1991 and 2020 at the N.N. Blokhin National medical Research Center of Oncology and A.S. Loginov Moscow Clinical Scientific Center.

Results. During the study, typical locations of metachronous tumors in patients who received treatment due to primary malignant tumors of the head and neck were determined, duration of development of multiple primary tumors, treatment methods and survival rates were analyzed.

Conclusion. Due to high risk of multiple primary tumors in patients who received treatment due to malignant tumors of the head and neck in the next 5 plus years, it is expedient to observe these patients during their whole lifetime. Considering typical locations of metachronous tumors, examination during dynamic observation should include instrumental methods such as panendoscopy. Surgical treatment should involve the whole spectrum of minimally invasive interventions including CO₂ laser surgery and transoral robot-assisted interventions.

Introduction. Current treatment of differentiated thyroid cancer includes surgical resection of the thyroid gland, radioiodine therapy (RIT) followed by hormone therapy with levothyroxine. If a patient has distant metastases, radioiodine therapy gains vital importance, becoming a non-competitive method of treatment. However, with incomplete expressed or lost ability of tumor cells to absorb radioactive iodine (¹³¹I), the effect of RIT occurs to be limited or completely lost. Radioactive iodine refractivity develops, in which the disease progresses despite ongoing therapy. Therapy with tyrosine kinase inhibitors for the progressive radioiodine-refractory thyroid cancer is currently the only recognized effective treatment. Based on the results of the SELECT study, in an indirect comparison with the data obtained earlier in the DECISION study, lenvatinib was found to be the most effective drug.

The study objective is to provide a comparative analysis of response to treatment and overall survival in two groups of patients with progressive metastatic differentiated thyroid cancer. In group 1, treatment was based on continuing radioiodine therapy in combination with suppressive hormone therapy with levothyroxine; in group 2, with the development of radioiodine refractivity, lenvatinib was prescribed.

Materials and methods. The study included two groups of patients treated at different times in the A.f. Tsyb medical Radiology Research Center - branch of the National medical Research Center of Radiology, ministry of Health of Russia. group 1 included patients who continued radioiodine therapy, despite disease progression on treatment (historical control group). This group (n = 191) consisted of patients with differentiated thyroid cancer who received radioiodine therapy until January 2015, when the criteria for radioactive iodine refractivity had not yet been established and there was no unified approach to such patients and no possibility of targeted therapy with tyrosine kinase inhibitors. group 2 (n =71) consisted of patients receiving lenvatinib in the 1st line targeted therapy from January 2015 to march 2022, from the time of radiographically confirmed tumor progression according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and establishing the fact of radioactive iodine refractivity.

Results. In the historical control group (n = 19) 18 (9.4 %) patients are alive to date. It should be specifically noted that all of them had a miliary dissemination in the lungs. None of the 191 patients had a complete or partial response to treatment. All patients had either disease stabilization (83 (43.45 %) patients), or disease progression (108 (56.54 %) patients). The number of RIT courses varied from 9 to 27, 13 ± 3.4 on average. The total dose for the entire treatment period varied from 21 to 75 GBq, 39.3 ± 10 on average. Overall survival averaged 80 ± 20.3 months (min 54 months, max 162 months). patients with slow disease progression had the longest overall survival. In the lenvatinib group the median duration of therapy in patients who discontinued treatment reached 26.3 months (1-52 months). Tumor response to treatment was evaluated in 71 patients. According to the RECIST 1.1 criteria, the maximum response was regarded as complete in 1 (1.41 %) patient, as partial - in 30 (42.45 %) patients, as stable disease - in 23 (32.39 %) patients, as disease progression - in 13 (18.31 %) cases. The median time to evaluate the first response to treatment was 4 (2-8) months. PFS was 17.3 months (95 % confidence interval 15.1-19.4 months). The median PFS in the subgroup of patients who responded to lenvatinib therapy (with a complete and partial response) was 32.5 months (95 % confidence interval 30.7-37.7). The median overall survival at the time of data analysis was not reached.

Conclusion. A comparative analysis showed that the approach to the treatment of patients with progressive radioyod-refracted differentiated thyroid cancer based on continued radioiodine therapy is wrong. It was the only impelled option when tyrosine kinase inhibitors therapy for differentiated thyroid cancer was unavailable. Currently, the majority of patients with progressive radioyodrefracted differentiated thyroid cancer receive lenvatinib in the first line targeted therapy. The role of this therapy in the treatment of patients with radioyodrefracted differentiated thyroid cancer is currently increasing. The promising prospects for the synthesis of new targeted drugs are becoming obvious, such as the need for further research and comparison of drugs already in use as well.

Introduction. Fine needle aspiration biopsy followed by cytological examination is the gold standard in the diagnosis of thyroid nodules. However, up to one third of cases represent an indeterminate result (Bethesda Thyroid Classification, 2017) III—V). Among such cases, category IV is the most common and most difficult to interpret (Bethesda, 2017). The study objective is to determination of the diagnostic and prognostic significance of the molecular genetic study of the fine needle aspiration biopsy material in patients with thyroid nodules with the cytological category Bethesda, IV.

Materials and methods. The study included surgical thyroid samples obtained from patients whose cytological examination revealed pathology of cytological category IV according to the Bethesda classification (2017). group 1 included surgical samples from 143 patients with thyroid lesions, and group 2 - cytological material from 45 patients. Determination of the BRAF V600E mutation, mutations in the RAS genes (KRAS, HRAS, NRAS) was carried out using allele-specific polymerase chain reaction, and the RET / PTC1, RET / PTC3 and PAX8 / PPARG translocations were determined using reverse transcription polymerase chain reaction. Sanger sequencing was used to detect mutations in the promoter region of the TERT gene.

Results. In group 1, an overall prevalence of the studied mutations in thyroid cancer was 35.1 %: 8.8 % of cases were mutation BRAF V600E, 24.6 % - mutations in the RAS genes, 1.8 % - mutation C228T in the TERT gene. The C228T mutation in the TERT gene was found in 1 case of widely invasive Hurtle cell carcinoma. The prevalence of mutations in benign formations was 4.7 %. mutations in RAS genes were also found in them in group 1, mutation BRAF V600E was associated with the presence of extrathyroid invasion (p = 0.024), vascular invasion (p = 0.018), and lymph node metastases (p = 0.018). In group 2, using the genetic panel sensitivity and specificity were equal: 36.4 and 93.9 %, respectively. positive and negative predictive values were 66.7 and 81.6 %, respectively. No RET / PTC and PAX8 / PPARG translocations were found in groups 1 and 2.

Conclusion. The investigated molecular genetic panel, having a high specificity for carcinomas, will make it possible to supplement the cytological diagnostics of material in the category Bethesda, IV. BRAF V600E was associated with an aggressive morphological pattern.

Introduction. The results of the calcitonin (Ctn) study in patients with thyroid nodules are included in the clinical guidelines for the treatment of differentiated thyroid cancer. However, the management of patients with moderately elevated Ctn up to 100 pg/mL is not clearly defined.

Materials and methods. The study included 103 patients with thyroid nodules and a Ctn level above the reference, but not more than 100 pg/ml. The Ctn concentration was determined using the Cobas e platform (Roche, Germany) or by the immunoradiometric method (Izotop, Hungary). 45 patients were operated on. The analysis of the incidence of medullary thyroid carcinoma (MTC), other thyroid and nonthyroid pathology in patients with elevated Ctn scan was carried out. The results of additional examination are presented: the serum cancer embryonic antigen, Ctn in wash-out, stimulated Ctn, gene RET mutation testing.

The study objective is to evaluate the probability MTC with Ctn level <100 pg/ml, propose management tactics for patients with elevated Ctn and negative cytological results.

Results. The incidence of MTC was 22 % (23/103). The maximum probability of mTC was at Ctn above 50 pg/mL (81 %, 13/16), at Ctn 31-50 pg/mL mTC was detected in 38 % (3/8). With Ctn <30 pg/mL and <20 pg/mL, the incidence of MTC was 9 % (7/79) and 6 % (4/64), respectively. In the majority of MTC patients (65 %), the tumor size did not exceed 1 cm. However, 22 % (5/23) had metastases to the neck lymph nodes. postoperative Ctn normalization was achieved in 96 % (22/23). In 26 % (5/19), a RET germ-line mutation was detected, most often p.val804met.

Among patients without MTC, other thyroid tumors were found in 35 % (28/80), more often papillary thyroid cancer (25 %, 20/80). 13 % (10/80) had other malignant neoplasms. parathyroid adenoma was detected in 3 % (2/80). The maximum Ctn in this group was in patients with chronic kidney disease and metastatic liver disease with cholestasis and ascites.

Cancer embryonic antigen was increased in 53 % of patients with MTC and in 7 % of patients without MTC. Ctn in washout was >2000 pg/mL in mTC and up to 938 pg/mL in patients with histologically confirmed absence of MTC.

Conclusion. If the Ctn level is <100 pg/mL and there is no cytological confirmation, the issue of surgery is decided individually, taking into account many factors. After excluding other causes of hypercalcitoninemia (hyperparathyroidism, kidney disease, other tumors), measurement of serum cancer embryonic antigen and Ctn in wash-out is recommended. In some cases, testing for a RET mutation can be helpful.

Introduction. pain syndrome significantly affects quality of life and daily activities of patients with cancer, especially at terminal stages of the disease. Opioid analgesics are considered the “gold standard” of therapy, but their use is associated with bureaucratic difficulties, as well as risk of a number of adverse events and drug dependency. Tafalgin is a Russian innovative tetrapeptide analgesic for subcutaneous injection. phase I and II clinical trials demonstrated its high effectiveness comparable to morphine and favorable safety profile.

The study objective is to evaluate the safety, tolerability, and pharmacokinetics of tafalgin after subcutaneous injection in healthy volunteers, as well as effectiveness and safety of varying doses in patients with pain syndrome due to malignant tumors.

Materials and methods. Phase I clinical trial included 39 healthy male volunteers. The drug was injected once subcutaneously at doses between 0.05 and 7 mg. plasma samples were obtained in the first 120 hours, and safety profile, tolerability and main pharmacokinetic characteristics of the pharmaceutical were determined. phase II clinical study included 42 patients with severe pain syndrome caused by malignant tumors who previously received morphine. At the 1^st stage (10 days), all patients were randomized in groups receiving tafalgin at doses 2, 3, 4, 5, 6 or 7 mg (dosing frequency was determined individually); at the 2^nd stage the patients were randomized into tafalgin (with dose determined at the 1^st stage) and morphine (with dose determined prior to the clinical trial) groups and received the medications for 7 days. Effectiveness and safety of tafalgin compared to morphine and pharmacokinetic parameters of the studied drug were evaluated.

Results. Tafalgin is characterized by fast absorption after subcutaneous administration (less than 30 minutes) which allows for fast clinical effect and absence of accumulation in the body. use of this pharmaceutical in patients with cancer allowed to maintain appropriate pain management achieved earlier through intramuscular morphine administration in 100 % of cases. Dynamics of mean daily pain intensity and necessity of additional analgesics did not differ between the groups. use of tafalgin did not require an increase in the dose or frequency of administration. Comparison of mean daily individual morphine and tafalgin doses showed that equianalgetic potential of the studied pharmaceutical was 1:3. Safety profile of tafalgin was favorable: adverse events during the trial were mild or moderate and not lifethreatening. use of tafalgin was associated with decreased number of opioid-induced adverse effects and improved quality of sleep in patients who previously received morphine parenterally.

Conclusion. Data obtained during the first in Russia clinical trial of a new selective pharmaceutical tafalgin with tropism to opioid pl-receptors definitively demonstrates its high effectiveness and safety and shows the necessity of further studies in this field.

This review presents data on the strategy for the treatment of oropharyngeal cancer associated with human papillomavirus. This pathology occurs mainly in young people without bad habits. Despite the low degree of differentiation, the course of the disease is relatively favorable. In addition, the tumor has a rather high sensitivity to conservative methods of treatment. The article discusses various options for de-escalation of therapy, modern drug regimens, as well as the results of the most significant randomized trials on this issue.

Various techniques for replacement of postresection defects of the orbit and periorbital zone in patients with malignant tumors are known, but clearly defined criteria for selection of the optimal variant have not been developed. This review considers current techniques of reconstruction of these defects using free revascularized grafts. Characteristics of various grafts, their advantages and disadvantages are described. Based on the analysis, algorithm of selection of the optimal methods of reconstruction for individual patients is proposed. The main criterion in selection of defect replacement techniques is the possibility of achieving the maximal functional and esthetic results.

Solitary fibrous tumors of the cerebral membranes are rare brain tumors. meningeal solitary fibrous tumors often metastasize outside the central nervous system, which significantly reduces the life expectancy of patients, while metastases can appear in a distant period after radical treatment of the primary intracranial tumor. The results of positron emission tomography combined with computed tomography with ¹⁸F-fluorodeoxyglucose and ¹⁸F-choline in 2 patients with different differentiation of solitary fibrous tumors were analyzed. The presented clinical cases demonstrate that clinical morphological variants of solitary fibrous tumors differ in aggressiveness and clinical course of the disease.