Background. The majority of tumors of the nasal cavity and paranasal sinus are diagnosed at an advanced stage, requiring invasive and mutilating surgery, and therefore, the reconstruction of post-surgical craniofacial bone defects using various implants is necessary.Purpose of the study: to evaluate the effectiveness of the use of the thin-profile implants made of titanium nickelide in the surgical treatment of nasal cavity and paranasal sinus cancers.Material and Methods. From 2002 to 2020, a total of 60 patients with stage Т3–4n0–1M0 nasal cavity and paranasal sinus cancer were treated at the Cancer Research institute (tomsk). All patients received radiation therapy followed by surgery with reconstruction of bone structures of the subcranial region and orbital walls. In the study group (n=30), the orbital walls were restored with individual thin-profile shape memory titanium nickelide implants. In the control group (n=30), typical porous and tissue titanium nickelide implants were used. They required adjustment during surgery and complicated reparative processes in the postoperative period due to their thickness. Tissue implants did not allow accurate restoration of the orbital walls due to their structure.Results. Surgical rehabilitation with orbital wall reconstruction using thin-profile titanium nickelide implants makes it possible to shorten the duration of surgery and improve the precision of surgical repair. Features of the architectonics of implants do not interfere with the growth of tissues of the recipient zone, thus preventing the development of inflammation in the implantation site. The technique allows adequate restoration of the natural position and function of the eye.

Localized and metastatic tumors are known to lead to the formation of circulating tumor cell (CTC ) clusters in the blood. Currently, there is a heightened interest in the study of molecular and biological characteristics of CTC s. Recent studies have shown the presence of different populations of CTC s in the blood of cancer patients. Some cells are cancer stem cells, some tumor cells undergo epithelial-mesenchymal transition (EMT), and most CTC s do not have features of either stem cells or EMT.The aim of the study was to evaluate the five-year metastasis-free survival rate in patients with invasive breast carcinoma, depending on the presence of various populations of circulating tumor cells in the blood before treatment.Material and Methods. A prospective study included 47 patients with newly diagnosed invasive breast cancer (T1–4N0–3M0), who were treated at Cancer Research Institute, Tomsk National Research Medical Center. The patients aged 31 to 69 years. The presence of different populations of CTC s in the blood of patients before treatment was determined by multicolor flow cytometry on the BD FACS Canto system, using different fluorochrome-labeled monoclonal antibodies to EpCam, CD 45, CD 44, CD 24, and N-cadherin. Five-year metastasis-free survival was evaluated by the Kaplan–Meier method. The differences were considered significant at p<0.05.Results. The results obtained demonstrated that the presence of both stem-like and non-stem CTC s showing signs of EMT with Epcam+CD 45-CD 44-CD 24-Ncadherin+, Epcam+CD 45-CD 44+CD 24-Ncadherin+, and Epcam(m)- CD 45-CD 44+CD 24-Ncadherin+ phenotypes in the blood of breast cancer patients before treatment reduced the five-year metastasis-free survival rate (p=0.0016, p=0.017 and p=0.011, respectively).Conclusion. Thus, CTC s in the EMT state are informative for liquid biopsy to assess the risk of hematogenous metastasis and can be considered as targets for selection of personalized chemotherapy.

Rehabilitation of patients after surgical treatment of maxillofacial cancer represents a major challenge and is the focus of attention in modem clinical oncology. The purpose of our study was to develop a personalized approach to the reconstruction of maxillofacial bone defects using bioceramic implants. We used 3D printing to customize bioceramic osteoimplants. These implants precisely fitted the anatomical shape of the maxillofacial region and had all strength characteristics. The presence of a bimodal pore structure of bioceramic implants favorably affected their integration ability. Fourteen reconstructive surgeries were performed in patients with maxillofacial tumors. In all cases, good cosmetic and functional results were achieved. Bioceramic implants meet all requirements for medical materials used in reconstructive surgery. The new technique of a personalized maxillofacial reconstruction using bioceramic implants can be safely used for cancer patients.

Surgical treatment is leading in the treatment of malignant tumors of the salivary glands. The complexity of the anatomical areas, the severity of the tumor process, the close location of the facial nerve branches lead to frequent complications in the postoperative period. The technique of elimination of paresis of mimic muscles with the use of a complex of therapeutic measures, including a course of physiotherapy with the appointment of a magnetolaser and SCENAR therapy developed at the Cancer Research Institute, Tomsk National Research Medical Center of the RAS and the prospect of its use in this pathology. The clinical case of application of this material is described.

Tumors of the nasal cavity and paranasal sinuses present a challenge to treat them. A combination of surgery and radiation therapy can improve treatment outcomes in 49-56% of patients with locally advanced nasal cavity and paranasal sinus cancer. The midface reconstruction poses a formidable challenge to the reconstructive surgeon due to the region’s complex skeletal and soft-tissue anatomy. The rehabilitation program including the reconstruction of the resected orbital walls using the porous and mesh implants from titanium nickelid (TiNi) was developed at the Cancer Research institute jointly with the Research Institute of Medical Materials. The technique was proven effective, allowing the natural position of the eye and visual function to be preserved in 90% of patients. A long period of reparative processes and risk of developing inflammation in the implant area, as well as the need to decrease length of surgery, contributed to the development of a novel approach to repairing the midface bone structures using the implant based on the microporous wire and TiNi mesh. Eighteen patients with nasal cavity and paranasal sinus cancer were treated using the combined thin implants. The novel technique allowed the time of the implant installation to be reduced to 5-10 minutes. The structure of the implant contributed to prevention of inflammatory processes in 97% of cases. Thus, the natural position of the eyeball and visual function were preserved in 100% of patients. The use of the TiNi implants in reconstructive surgery for patients with nasal cavity and paranasal sinus cancer led to reduced time of surgery and rehabilitation, increased level of social adaptation of patients and improved cosmetic and functional results.

At the Cancer Research Institute together with the Research Institute of Medical Materials and Tomsk State University, various types of implants from titanium nickelid (TiNi) were developed for the reconstruction of skull bone defects. Between 2000 and 2015, a total of 43 patients with malignant and benign calvarial and skull base tumors were treated. All patients underwent surgery alone or in combination with other treatment modalities. Fifty surgeries with primary reconstruction of calvarial and skull base defects using individually fabricated TiNi implants were performed. Our techniques for the reconstruction of postoperative skull bone defects appeared to be highly effective: restoration of supporting structures was achieved in 100% of cases, stability in 96% of patients, integrity and barrier function in 90% of cases. The TiNi implants have high mechanical strength and biocompatibility. No cases of fragmentation and rejection of the implants were registered.

The preliminary treatment outcomes for 8 patients with sinonasal carcinoma have been presented. All the patients received a multimodality treatment including thermoradiotherapy followed by the operation and intraoperative radiotherapy. Clinical testing of the method of the combined treatment of sinonasal carcinomas with local hyperthermia has showed that the positive effect was achieved in all patients without causing pronounced complications during the treatment. Further studies with careful quality control are required to solve the existing problems of local hyperthermia in the head and neck region before this method of treatment can be recommended for a wide clinical application.

Резюме: Комбинированное лечение с использованием ИОЛТ (интраоперационная лучевая терапия) предполагает максимально радикальное удаление основного опухолевого процесса, а возможные микрофокусы рака в прилежащих тканях, оставшиеся микрометастазы девитализировать с помощью интраоперационного облучения, основной точкой приложения которого является область большего онкологического риска. Помимо этого, использование ИОЛТ позволяет сократить время лечения и значительно снизить лучевую нагрузку на кожу и критические органы при сочетании с наружным облучением. Ключевым моментом при планировании ИОЛТ является правильный выбор однократной дозы, кроме того, при сочетании с ДГТ (дистанционная гамма-терапия) необходимо решить вопрос об изоэффективности их воздействия на нормальные ткани. Величина суммарной курсовой дозы смешанного облучения ИОЛТ и ДГТ не должна превышать 60–65 иГр, или в показателях фактора ВДФ 100–125 усл. ед. в очаге-мишени. В Томском НИИ онкологии разработана методика комбинированного лечения злокачественных опухолей полости носа и придаточных пазух с предоперационным курсом фотонной терапии в режиме среднего фракционирования дозы, последующим хирургическим вмешательством и ИОЛТ на ложе удаленной опухоли. Однократную дозу ИОЛТ определяли по формуле. Интраоперационная лучевая терапия проводилась на малогабаритном бетатроне МИБ-6Э с энергией 6 МэВ, разовая очаговая доза равнялась 10–12 Гр. Доказательства эффективности применения ИОЛТ получены при клинической апробации метода. Проведено лечение 115 больных раком полости носа Т3–4. Лечение удовлетворительно перенесли все больные. Анализ локализации рецидивов после комбинированного лечения с ИОЛТ и ДГТ показал, что дополнительное облучение зон «риска» в операционной полости позволяет снизить частоту рецидивов в этих зонах и существенно повлиять на показатели выживаемости больных. Показатели 5-летней безрецидивной выживаемости в основной и контрольной группах составили 66,2 ± 8,8 % и 40 ± 9,2 % соответственно. Накоплен собственный клинический опыт, осуществлена методологическая и методическая разработка проведения интраоперационного облучения. Проведенные исследования продемонстрировали безопасность доставки ИОЛТ при лечении пациентов с локально развитым раком головы и шеи в контексте агрессивной комбинированной терапии.

Obvious advantage of IORT (intraoperative radiotherapy) is that the radiation source is delivered directly to the bed of the tumor during surgery, thus avoiding the negative impact on the skin, subcutaneous tissue and reducing the risk of fibrosis. Sinonasal tumors-a convenient object for intraoperative radiotherapy application (surface location, relatively small size tumors, good operational access). The surface location and comparatively small size of neoplasms, good operational access provide an efficient and accurate transfer of the electron beam to the postoperative cavity to increase the irradiation dose in the areas of the most probable recurrence, which makes the tumors of this localization a convenient object for the use of the intraoperative radiation therapy. The treatment was conducted using a mobile compact betatron (MIB-6E), 10-12 Gy single dose. IORT session extends surgery period by 30 min. There were no pathological clinical and laboratory reactions on IORT in the early postoperative period. Carrying out the procedure is possible in various standard operating rooms. It does not require special security measures for the patients and the staff. IORT with the help of electron beam allows avoiding post-radiation reactions and achieving a 5-year-disease-free survival of 66% of the patients. IORT session is possible through a minimal incision during organ preservation surgeries. Evident economic feasibility provides the prospects of applying IORT in the clinical practice.

Preliminary treatment outcomes for 35 patients with stage T1–3N0–2M0 laryngeal and laryngopharyngeal cancer have been presented. Out of 35 patients, there were 30 with laryngeal cancer and 5 with laryngopharyngeal cancer. Combined modality treatment including preoperative radiation therapy was administered to 16 patients and radical radiotherapy (without surgery) was given to 19 patients. Radiotherapy response was assessed in patients treated with total doses of 40 Gy and 60 Gy. Local hyperthermia resulted no in expressed general and local reactions. Patients with laryngeal and laryngopharyngeal cancer and tumor regression of less than 50 % or stable disease underwent surgery. Histological examination revealed complete response in all cases. Patients with laryngeal and laryngopharyngeal cancer and tumor regression of more than 50 % received radical radiation therapy in combination with local hyperthermia. The analysis of treatment outcomes indicates that local hyperthermia allows the rate of complete response to be increased.

Cancer of the larynx and laryngopharynx, which is accessible to visual and instrumental examination, remains the most relevant and complicated problem among head and neck malignances as before. Investigations show that the incidence of cancer at these sites in Russia in the last decade has risen from 4.5 to 9.67 %. This is a severe and poor prognostic form of cancer, which is characterized by its nonspecific early clinical manifestations, complex anatomic and topographic structure, and a high rate of regional metastases. The mainstay of treatment for head and neck cancer involves 3 components: surgery, chemotherapy, and radiotherapy (RT), which are performed alone or in combination. The most commonly used technique is combined, frequently crippling due to organ-removing operations. The clinical introduction of current radio modifiers, local and deep hyperthermia systems, is a promising approach to improving the results of treatment, to enhancing the radiation damage of RT, and to achieving the tumor regression sufficient for surgical intervention without augmenting the early and late toxicity inherent in chemoradiation treatment. The results of the performed study of 35 patients with T2–3N0–2M0 laryngeal and laryngopharyngeal cancer proved the high efficiency of local hyperthermia in treating malignancies in this region during both preoperative (grades III– IV therapeutic pathomorphism) and radical beam RT.

Preliminary treatment outcomes for 35 patients with stage T 1-3N 0-2M 0 laryngeal and laryngopharyngeal cancer have been presented. Out of 35 patients, there were 30 with laryngeal cancer and 5 with laryngopharyngeal cancer. Combined modality treatment including preoperative radiation therapy was administered to 16 patients and radical radiotherapy (without surgery) was given to 19 patients. Radiotherapy response was assessed in patients treated with total doses of 40 Gy and 60 Gy. Local hyperthermia resulted no in expressed general and local reactions. Patients with laryngeal and laryngopharyngeal cancer and tumor regression of less than 50 % or stable disease underwent surgery. Histological examination revealed complete response in all cases. Patients with laryngeal and laryngopharyngeal cancer and tumor regression of more than 50 % received radical radiation therapy in combination with local hyperthermia. The analysis of treatment outcomes indicates that local hyperthermia allows the rate of complete response to be increased.

Results of surgical treatment of 33 patients with tumors growing into the cranial cavity were analyzed. All patients underwent primary reconstruction of defects of the calvarium and/or skull base using individual titanium nickelid implants. Stereolithographic model was used as a template for manufacturing individual implants. Application of individual endoprosthesis from porous titanium nickelid for replacement of postoperative defects of the skull in cancer patients allowed the length of surgery to be decreased and the period of wound healing to be shortened affecting no short-and long-term results

This review presents the experience in diagnosing 62 patients with stage T1-2N0-2M0 laryngeal and laryngopharyngeal cancers. All patients underwent a comprehensive examination. Spiral computed tomography with intravenous bolus contrast allowed the primary tumor and surrounding tissues to be effectively assessed before treatment and after 2 courses of chemotherapy. The analysis shows that spiral computed tomography with intravenous bolus contrast may be considered reasonable in assessment of results of preoperative chemotherapy used in combined modality treatment for laryngeal and laryngopharyngeal cancers because it allows the extent of primary tumor regression to be determined.