Background. Approximately 10 % of patients with well-differentiated thyroid cancer (WDTC) develop distant metastases. Of them, only 23 % have bone metastases. Complications associated with metastatic lesion in the skeleton significantly affect overall condition of patients and their quality of life. Surgery and pharmacotherapy are highly traumatic and toxic. Bisphosphonates are stable structural analogues of pyrophosphate that inhibit osteoclast activity, thereby reducing bone resorption, which increases the time to development of bone complications, improves patient’s quality of life, and reduces pain.

The study objective is to assess performance status and pain severity in WDTC patients with distant bone metastases after bisphosphonate therapy.

Materials and methods. We analyzed clinical experience in using bisphosphonates in WDTC patients treated in P.A. Herzen Moscow Oncology Research Institute between 2016 and 2020. This study included 41 patients with WDTC and bone metastases of various locations. Pain severity was evaluated using a 5-point verbal scale; performance status was evaluated using the Eastern Cooperative Oncology Group scale.

Results. We observed an improvement in patients’ performance status (from score 2 to 0 according to the Eastern Cooperative Oncology Group scale) in response to therapy. We also found a decrease in pain intensity (from score 4 to 1.5).

Conclusion. The inclusion of bisphosphonates into the treatment scheme for WDTC patients with bone metastases can reduce pain intensity and improve performance status.

Background. Parathyroid cancer (PC) is extremely rare, usually diagnosed after surgery, there are no clinical recommendations for the treatment of metastatic PC.

The study objective is to present the results of a clinical examination and treatment of patients with PC.

Materials and methods. Retrospective analysis of 15 PC patients treated from 2001 to 2019. The results of laboratory tests, the surgical approach, the results of treatment, the rate of metastasis and relapse within 19 months (3 months – 11.6 years) after surgery are presented.

Results. Tumor size is 35 mm (20–45 mm). Lymph node metastases – 1 (6.7 %), distant metastases – 2 (13 %). The median initial parathyroid hormone (PTH) is 735 pg/mL, calcium 3.22 mmol/L. Severe hyperparathyroidism with osteitis fibrosa cystica – in 6 (40 %). The surgical approach was parathyroidectomy in 10 (67 %), en bloc resection in 5 (33 %). Normalization of PTH and calcium after surgery – 13 (87 %). In two patients with distant metastases, the PTH and calcium remained high. A patient with Th6 vertebral metastasis was successfully operated on, with normalization of PTH and calcium, and 1.5 years was without relapse. A patient with lung and liver metastases received sorafenib after surgery, with decrease in calcium level. She died of progression 12 months after operation. Among patients with normalization of postoperative PTH, one had local relapse after 4 years. The patient was re-operated and 1 year after the second operation without relapse. The remaining patients are without relapse/progression.

Conclusion. At the time of diagnosis, lymph node metastases are in 6.7 %, distant metastases – 13 %. Normalization of PTH and calcium after surgery suggests a good prognosis, but does not exclude the recurrence in the future, which requires long-term follow-up. Repeated surgery for local recurrence or solitary distant metastases can provide stable remission. Sorafenib in metastatic PC has managed to control hypercalcemia in the short term, however, antitumor efficacy requires further study.

The study objective is to summarize clinical experience in the treatment of esthesioneuroblastoma (ENB) accumulated by specials at N.N. Blokhin National Medical Research Center of Oncology.

Materials and methods. We analyzed the data of 115 ENB patients who had undergone treatment between 1965 and 2019.

Results. The 15-year overall survival rate was 1.2–1.7 times higher in patients receiving comprehensive treatment (47.7 ± 11.3 %) than in those receiving other types of therapy. In addition to that, comprehensive treatment ensured the highest rates of 3-year, 5-year, and 10-year relapse-free survival (49.3 ± 11.8 %), as well as the longest median survival (7.2 years). Chemoradiotherapy was effective in 34.8 % of patients with locally advanced ENB, while in 9 out of 45 patients (20.0 %), it resulted in partial response, which suggest that such treatment can control aggressive disease course and increase survival. Surgical treatment (alone or in combination with chemotherapy and radiotherapy) was indicated for 64 patients. However, only in 43 of them (67.1 %), it was performed as originally planned. Five patients (7.8 %) had partially radical surgeries and sixteen patients (25.1 %) had non-radical surgeries.

Conclusion. The most effective treatment strategy for locally advanced ENB is a combination of surgery, chemotherapy, and radiotherapy. Chemoradiotherapy at the first stage followed by surgery was found to be an optimal treatment scheme. Tumor sensitivity to chemo- and radiotherapy affects both short-term and long-term treatment outcomes. Partially radical surgeries for locally advanced ENB are acceptable if conservative treatment is planned after operation. Treatment strategy should depend on the tumor spread (stage), grade, and proliferative activity, as well as patient’s age, somatic status, and comorbidities. Multivariate analysis has demonstrated that none of treatment methods decrease survival. The most significant factors negatively affecting the prognosis were as follows: T3–4 tumor, involvement of regional lymph nodes before treatment initiation, distant metastasis, grade IV tumor, and Ki-67 index >21 %.

The immune system plays a key role in the development and progression of head and neck squamous cell carcinoma. Understanding the dysregulation and blockage of the immune system of malignant tumors in this location can improve treatment outcomes. A special group is made up of patients who have a widespread process and relapse after chemotherapy with platinum drugs, because they have a very poor prognosis and limitations in the possibilities of further treatment. To date, the most important data relate to drugs acting on the PD-1 (programmed cell death protein 1)/PD-L1 (programmed death ligand 1) immune checkpoints, which are used by the tumor to block the immune system, which have allowed to increase the effectiveness of treatment. The article presents a clinical case demonstrating the effectiveness of the use of checkpoint inhibitors after the use of platinum preparations.

The tall-cell variant of papillary thyroid carcinoma is a rare malignancy characterized by an aggressive course, low relapse-free survival, early metastasis, and frequent development of radioiodine refractoriness. We report two cases of tall-cell papillary thyroid carcinoma in patients who had disease progression after combination treatment and started to receive lenvatinib. We observed partial and complete regression of metastases in response to lenvatinib. Our findings are consistent with the results of other studies assessing treatment efficacy for disseminated tall-cell papillary thyroid carcinoma.

Introduction. The term “local recurrence” is usually understood as regrowth of a tumor after surgical treatment. The regrowth appears within 3–5 cm from postoperative cicatrix. The causes for such prolonged tumor growth or recurrence of patients with cutaneous melanoma are nonradical surgical treatment as well as satellite or transit metastases that were not removed in-block with primary tumor. A great number of clinical researches, aimed at examination of melanoma, its patterns, anatomical criteria and features of clinical course, gave an opportunity to separate satellite or transit metastases into an independent group. Such metastases are realized inside or subdermally, up to 2 cm or more than 2 cm from the primary tumor, yet, not reaching the location of the first regional barrier.

The aim of the study is to define influence of the main prognostic factors such as tumor thickness according to Breslow, the level of invasion according to Clark and the presence of ulceration on the frequency of local recurrence with cutaneous melanoma of head and neck.

Materials and methods. The research involved 174 patients with cutaneous melanoma of head and neck (1995–2014). According to our index of contraction of a skin flap (median 30 %) the true borders of resection were clearly defined within all the patients. Thereby, 3 groups were identified with the following resection margin: 1.0 cm, where followed-up treatment results were analyzed.

Results. Progression-free survival didn’t correlate with the size of surgical resection margins. The survival rates were the best with the lowest resection margin under 0.5 cm (77.3 %) and the worst with the highest resection margin more then 1.0 cm (38.7 %). That means that the treatment results don’t depend on the width increase of tumor resection margin.

Conclusions. We consider that clear surgical margins for any thickness of cutaneous melanoma of head and neck should be as follows: 4 mm – 0.72 mm (p = 0.016). In our work, the influence of the main prognostic factors, such as tumor thickness according to Breslow, level of invasion according to Clark and ulceration on the frequency of head and neck cutaneous melanoma local recurrences had no impact.

Introduction. Standard methods of drug or radiation therapy administration for salivary gland cancer is the least successful for now. Therefore, the identification of new markers with morphological features is extremely necessary to improve the effectiveness of treatment and increase the survival rates of patients with this pathology.

The study objective is to assess the prevalence of expression of HER2/neu, PD-L1, and RET mRNA in salivary gland malignancies and assess their impact on overall and disease-free survival.

Materials and methods. Fifty-nine patients with a confirmed diagnosis of salivary gland cancer (stages II–IVA) were examined in the period from 2012 to 2014 at Saint Petersburg City Clinical Oncology Dispensary. All materials were subjected to immunohistochemical research to determine the expression of HER2, PD-L1 in tumor and immune cells, the CPS index was calculated, and the frequency of the mRNA gene RET expression using a real-time polymerase chain reaction was detected.

Results. The overall survival of patients with mild and high HER2 expression was 41 months (95 % confidence interval (CI) 4.50–72.00), which is more than 4 time less than in patients with low or no expression (p = 0.00715). Significant differences were also received in the progression-free survival in the group of patients with negative or insignificant expression of HER2 receptors. The overall survival of patients with CPS >1 was 72 months (95 % CI 19.5–72.00) and significantly differed from the group of patients with CPS <1, where it was not yet achieved (p = 0.0124). mRNA expression of the RET gene was detected in 13 out of 48 cases, which was 27.08 %. The expression level ranged from 0 to 0.205. The progression-free survival in the group of patients with mRNA expression was 168 months (95 % CI 16.00–168.00) and tended to increase in the group of patients who did not have this expression.

Conclusion. When analyzing the obtained data, it was proved that knowledge of the salivary glands malignant tumors receptor status become one of the factors in determining the prognosis of the disease, as well as a predictive factor of targeted drugs effectiveness (after сonducting prospective randomized studies).

Oral mucositis is one of the most common effects of chemoradiotherapy in patients with oropharyngeal cancer. The development of oral mucositis is the main cause of interruption of antitumor therapy, which significantly affects the results of treatment of the main disease. Despite the fact that the disease is well studied in the literature, today there is no universal treatment and prevention protocol. The aim of this review is to analyze scientific publications devoted to the problems of etiology, pathogenesis, clinic, diagnosis, treatment and prevention of oral mucositis.

One of the main problems of nasopharyngeal carcinoma treatment is the high incidence regional and distant failures. The method of choice in the first line therapy for the primarily diagnosed nasopharyngeal carcinoma is chemoradiotherapy with poor success rate. The main etiological factor in the occurrence of nasopharyngeal carcinoma is the Epstein–Barr virus, which DNA’s copies could be detected in blood samples in patients with nasopharyngeal carcinoma, which may indicate tumor activity. The indicators of these titers reach different values depending on the stage of the tumor process, the presence of distant metastases, individual patient parameters, and the tumor response to the therapy. Given the high specificity of this biological marker, it is necessary to consider the possibility of its use as a prognostic indicator for assessing the success of the selected method of conservative treatment, as well as assessing the prognosis.

Background. Currently, the proportion of pregnancies obtained by assisted reproductive technologies (ARTs) reaches 1.7–4.0 %. Short-term and long-term results of ART implementation require public and, most importantly, legal assessment. Some publications suggest higher risks of congenital deformities and head and neck cancers in children conceived by ART.

Objective: to review publications analyzing the problem of head and neck cancers in children conceived by ART and legal protection of the embryo.

Materials and methods. We performed retrospective analysis of 42 articles published in 1995–2019, including 33 foreign and 9 Russian articles.

Results. Earlier studies have demonstrated that children conceived by ART have an increased risk of cancers, including head and neck cancers, such as central nervous system tumors and retinoblastoma. Recent publications have shown no significant differences in the prevalence of malignant tumors between children born after ART and children conceived naturally. Nevertheless, the risk of developing head and neck tumors is higher in children after ART. The analysis of Russian and international legislation has demonstrated that the legal status of an embryo differs depending on whether it develops in vivo or in vitro.

Conclusion. Children conceived by ART are at higher risk of malignant head and neck tumors, primarily central nervous system tumors and retinoblastoma. The legal status of an embryo depends on whether it develops in vivo or in vitro.

Background. Reconstruction of subtotal and total defects of maxillofacial region after ablative tumor surgery is a challenging task of reconstructive surgery. The “golden rule” is maintaining of radicalism of ablative surgery as well as appropriate surgical reconstruction and prosthodontic rehabilitation, that allows patient return to normal life. Wherein reconstructive procedure is focusing on restoring of mandibular continuity by the means of different flaps and grafts, while prosthodontic rehabilitation is performing after some period of time (usually around year) by the means of removable and non-removable prosthodontic devices. Non-removable device requiring dental implants insertion into grafted material followed by period of osteointegration, that is requiring some time as well. However, within this period of time one could observe significant soft tissue deformity.

The objective is to improve the outcomes of surgical reconstruction of extensive defects of the mandible and to carry out rapid prosthodontic rehabilitation supported by dental implants by application of 3D preoperative planning and navigation devices.

Clinical case. Forty-nine years-old female patient with recurrent ameloblastoma, that affects vertical and horizontal ramus of the mandible. Within virtual preoperative planning one performed: resection of the mandible associated with exarticulation of condylar head, virtual plate bending according to contours of the mandible (that were determined by application of “mirror” function of virtual planning software), arthroplasty of temporomandibular joint, determination of donor site on fibula bone, osteotomy of fibula free flap, positioning of dental implants, transferring of composite flap and it’s fixation by reconstructive plate. According to acquiring data one performed fabrication of patient specific navigation guides for both fibula flap segmentation and dental implants positioning. Surgical procedure included single-step tumor ablation and exarticulation of condylar head, reconstruction of defect by the means of osseo-myo-cutaneous fibula free flap, that was pre-implanted by dental implants, total joint reconstruction by titanium condylar head and polypropylene fossa, fixation of the flap and condylar head in recipient site by the means of prebended reconstructive plate, as well as insertion of non-removable bridge prosthodontic device. Postoperative result was asses clinically and radiologically. No significant postoperative complications occurred. Restoration of facial contours, mouth opening, I class occlusion, as well as adequate meal and speech were detected. Postoperative radiological investigation revealed adequate positioning of dental implants within neo-mandible, as well as positioning of artificial joint.

Conclusion. In cases of extensive tumors of the jaws single-step ablative surgical procedure, reconstruction of missing anatomical structures of the jaws and simultaneous prosthodontic rehabilitation allows to prevent possible deformities of the soft tissues and due to rapid restoration of vital functions has great impact to quality of patient’s life. Adequacy of performing procedures could be reached by implementation of virtual preoperative planning and fabrication of patient-specific surgical guides.

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer among head and neck malignancies and causes of cancer death. More than 50 % of patiens have relapses within first 3 years after treatment, with median survival less than 6 months. Cetuximab is the first targeted agent for HNSCC, is considered as alternative regiment in case of intolerance to platinum-based chemotherapy, and also can activate an antigenspecific T-cell immunity in head and neck cancer patients. Nivolumab is a check-point inhibitor, that improves overall survival of patients with advanced recurrent/metastatic HNSCC, due to the CheckMate-141 study results. The results of phase II study сoncurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC showed a benefit for patients without prior check-point inhibitor exposure and overall well tolerated. Thus, we have 6 cases of HNSCC, treated with combination of nivolumab and cetuximab, resulted in durable (12 months) partial response or stabilization without severe adverse events. In our study, all 6 patients had prior check-point inhibitor exposure with nivolumab. Cetuximab was added to a treatment protocol after evidence-based progression during check-point inhibitor therapy. We demonstrate a case report of recurrent locally advanced HNSCC, treated with combination of nivolumab and cetuximab and resulted in stabilization. Only 1 patient had a progression after concurrent targeted and immune-therapy with nivolumab and cetuximab. New combination was well tolerated without severe adverse events. To our opinion, first results are challenging and we believe in great perspectives of comprehensive molecular profiling and combination of targeted and immune-therapy for better results.