Preoperative stereotactic ablative body radiotherapy with postoperative conventional irradiation of soft tissue sarcomas: Protocol overview with a preliminary safety report.

Preoperative radiotherapy in patients with soft tissue sarcomas is characterized by important advantages: high precision of dose delivery, reduction of tumor volume and implantation potential, induction of immunologic response. Postoperative irradiation is associated with a reduced risk of complication, and a comprehensive radiotherapy planning in accordance with the pathologic report. Combination of pre- and postoperative irradiation gives the opportunity to use the best of both methods. OBJECTIVE: To analyze feasibility and safety of radiotherapy protocol that combined pre- and postoperative radiotherapy in patients with soft tissues sarcomas of extremities. MATERIALS AND METHODS: From 06.2018 to 01.2021, 23 patients with soft tissue sarcomas of extremities were included in the protocol (NCT04330456) and 14 cases with at least 12 months follow-up were eligible for analysis. Preoperative stereotactic ablative body radiotherapy (SBRT) was performed as 5 fraction of 7 Gy with dose reduction (5 fractions of 5 Gy) on the margins of the tumor. Postoperative radiotherapy started 5-8 weeks after the surgery and was performed as standard compartmental irradiation in 25 fractions of 2 Gy. Complications were determined according to CTCAE and wound complication scales. RESULTS: Preoperative SBRT and subsequent radical resection with tumor free surgical margins were performed in all 14 cases. Primary wound closure was mentioned in all patients. Postoperative radiotherapy started 51.8 days (range 33-99 days) days after the surgery. With a relatively short follow-up of 21.5 (13-30) months, we recorded 2 cases (14%) of severe complications (Canadian sarcoma group criteria), and there were no local recurrences. CONCLUSION: Our preliminary results demonstrate that the combination of preoperative SBRT and postoperative conventional radiotherapy is feasible and does not increase the risk of postoperative complications.

[New approaches to treatment for malignant tumors using perfusion technologies].

The paper summarizes and analyzes the results of complex treatment of patients with malignant tumors performed in the N.N.Petrov Research Institute of Oncology using perfusion technologies. Safety and efficacy data on various chemoperfusion is presented: intraperitoneal chemoperfusion combined with cytoreductive surgery in patients with locally advanced and disseminated gastric cancer, recurrent ovarian cancer and pseudomyxoma peritonei; isolated lung perfusion combined with metastasectomy in patients with lung metastases; isolated limb perfusion with/without cytoreduction in patients with locally advanced skin melanoma and locally advanced soft-tissue sarcoma. The conclusion is made that both intraperitoneal and isolated chemoperfusions are not associated with higher incidence of intra- and postoperative morbidity. However safety of the procedures could be increased through optimizing tactics of surgical procedures prior to chemoperfusions. The use of perfusion technologies provides significant survival advantage in patients who can't benefit from conservative treatment.

Subungual melanoma. Features of clinic, diagnostics and treatment.

Subungual melanoma (SM) is a rare tumor and is 3-5% of all malignant skin melanoma. There was analyzed database of the Population-based Cancer Registry of the N.N.Petrov Research Institute of Oncology of St. Petersburg, the first in Russia, including information on more than 2,500 patients with malignant melanoma, of which for the period from 1986 to 2014 there were selected cases of acral lentiginous melanoma - 85 patients (3.4%). This group included 40 patients with SM (1.6%). More than half of patients were referred to a specialist in a year since the appearance of the first symptoms of the disease. Distribution of SM patients by Stages was as follows: 30% (n = 12) cases of the disease were identified in the Stage I, 40% (n = 16) - in the Stage II, 25% (n = 10) - in the Stage III and 5% (n = 2) - in the Stage IV. The most commonly misdiagnosed cases were considered as inflammation, fungal or other lesions of the nail phalanx. Histologically SM patients met all morphological types of melanoma. Over half of patients had Clark IV and V levels of invasion. The mean value of tumor by Breslow thickness was 5.5 mm. All patients with SM underwent radical surgery in the following volumes: 75% (30 cases) - amputation at the middle level (n = 16) and basic (n = 14) phalanges; 20% (8 cases) - disarticulation at the level of the proximal interphalangeal (n = 6) and metatarsusphalanx (n = 2) joints; 5% (n = 2) - resection metacarpal and metatarsal. Inguinal-femoral lymphadenectomy was performed in 8 patients with metastatic lesion of regional lymph nodes.

Leiomyosarcoma of soft tissues. Clinical characteristic and results of treatment.

Clinical characteristics of leiomyosarcoma of soft tissues and results of treatment of patients with this pathology are presented. It was revealed that the peak of incidence was in the age group 5O-69 years. There was showed the priority of surgery, as the only method of treatment, and in the combined regimen with the overall five-year survival of 43,2% and 33,3% respectively.

[COMPARATIVE EVALUATION OF SURGICAL APPROACHES TO TREATMENT OF PATIENTS WITH SKIN MELANOMA].

In recent years there has been rapid growth in the incidence of melanoma. Due to the large number of patients with various pigmented lesions, suspicious for melanoma, requiring differential diagnosis there is an actual problem of excisional biopsy in this group of patients. This review extensively covered approaches to radical surgical treatment of patients with skin melanoma. There are described in detail results of the studies of foreign experts regarding the influence of excisional and incisional biopsy on overall and disease-free survival rates of patients. On a large representative material (1126 patients) there are widely reflected the results of our studies to assess the effect of different surgical approaches to treatment of patients with skin melanoma. At present the authors can not recommend to perform excisional biopsy of patients with primary skin melanoma in oncological practice. Obviously for a final resolution of this problem it is necessary to conduct a multicenter randomized trial.

[PERFUSION TECHNOLOGIES IN TREATMENT OF PATIENTS WITH SKIN MELANOMA AND SOFT TISSUE SARCOMAS OF EXTREMITIES].

A steady increase of incidence of skin melanoma and soft tissue sarcomas of the extremities currently continues to be observed. Taking into account the high probability of developing of locally disseminated forms of skin melanoma and soft tissue sarcomas of extremities, the need to use combined methods in their treatment is quite high. In the 21st century the possibility of a use of isolated regional chemoperfusion provides a high objective response of tumor to chemotherapy without their systemic impact and improves the quality of life through preservation of the limb. This review describes the currently used drugs, and the results of ongoing clinical research in the world, as well as the results of our own study.

[Melphalan pharmacokinetics during isolated limb regional perfusion in patients with skin melanoma and soft tissue sarcoma].

The study of pharmacokinetics of melphalan in the perfusate and blood plasma during isolated limb regional perfusion (ILRP) was carried out in patients with melanoma (n=21) and soft tissue sarcoma (n = 24). Melphalan was administered as 10 mg/l for a lower extremity and 13 mg/l for a upper extremity. Quantification of melphalan in perfusate and blood samples was performed by means of liquid chromatography/tandem mass spectrometry. 30 samples of the perfusate and 27 venous blood samples were analyzed. During the first 5 minutes of ILRP concentration of melphalan in the perfusate decreased to 13.2% of the initial value, and by the end of perfusion (60 minutes) it was 3.3%. The amount of melphalan in the blood plasma of the patients by the end of ILRP wasn't higher than 1.6% from the administered dose. That demonstrates minor systemic absorption of the drug during ILRP. Moreover melphalan concentration in the blood plasma during the perfusion was in average 0.015-0.223 mg/l which is significantly lower compared to the blood plasma concentrations after intravenous administration of melphalan. Thus ILRP procedure provided 97% of the melphalan dose accumulation in the soft tissues of a limb and in tumor tissues. Also pharmacokinetic advantage of melphalan over systemic administration of the drug was shown.

[The gastrointestinal stromal tumor of the stomach in child: characteristic of diagnostics].

The observation of stromal gastric tumor of 12 years old girl has been investigated. The diagnostics was carried out on tumor biopsy taken by a laparoscopy. An evident edema of stroma caused "pseudo-papillary" organization of epithelioid cell neoplasm prevented the right diagnosis established only by immunohistochemical staining of CD117 and CD34 markers. The absence of mutations in C-kit and PGFRA genes uncovered by molecular-genetic analysis is typical for stromal gastric tumors in child. The next gastric resection allowed to estimate tumor appearance and localization, histological organization, and to repeat immunohistochemical studying. This observation confirmed the correctness of diagnosis and established high level of Ki67 proliferative activity (12-15%) determined prescriptions of target medicamental therapy.