№85. Нерешенные вопросы хирургической онкологии

Nowadays surgery is still the mainstay of solid tumors treatment. En Bloc resection is surgical treatment in amount of complete tumor removal. There remains considerable uncertainty about many aspects of resection boundaries, including definition and influence of anatomical and histological factors. One of the biggest challenges for the surgeon is choosing the right surgery for the «right» patient, taking into account the type of tumor and its biology.

Keywords: surgery, en bloc resection.

Morbidity and mortality from colorectal cancer remains high in the world, despite the undoubted success in the treatment of this pathology in recent years. The main cause of death is the progression of the disease in form of metastatic process. In this clinical group it is impossible to apply a standardized approach to treatment due to many different options for the course of the pathological process, which requires a constant search for a solution to the problem and selection of effective treatment options. The aim of this review was to investigate the feasibility of performing palliative surgery for rectal and colon cancer and their impact on overall survival and treatment efficacy. There is no doubt that there is a need for large RCTs.

Keywords: colorectal cancer, hepatic metastases, palliative surgery, overall survival.

Aim: to study the effectiveness of the use of transarterial chemoembolization (TACE) in the treatment of patients with metastatic uveal melanoma.

Material and methods: in N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia in the period from 2000 to 2019 72 patients received treatment (TACE) for metastases of uveal melanoma in the liver. Of these: men – 22 (30,6%), women – 50 (69,4%). Average age 46,28±10,32 years, range 23–84 years. The time of detection of metastatic liver lesions after treatment of the primary tumor ranged from 2 to 252 months, the median was 24 months. The volume of liver damage was up to 25% in 19 patients, from 25% to 50% in 33 patients, from 50% to 75% in 20 patients. A total of 134 TACE interventions were performed. Depending on the volume of the lesion, the nature of the blood supply to the tumors and the response to treatment, patients underwent 1 to 5 sessions of TACE: in 27 patients one TACE, in 35 – two, in 5 – three, in 3 – four, and in 2 – five TACE. As an embolizing component, lipiodol 10 ml was used in 106 cases, microspheres in 16 cases (particle sizes varied from 100 to 500 μm), in 12 TACEs, combinations of the presented embolizing materials were used. Carboplatin, doxorubicin or gemcitabine were used as chemotherapy drugs.

Results: 58 patients (80,6%) had a moderate postembolization syndrome, expressed by pain, febrile temperature, nausea, and vomiting. A local response (including complete response, partial response, or stabilization by mRECIST criteria) was observed in 53/72 (73,6%) patients with metastases of uveal melanoma. The duration of observation of patients after TACE was from 2 to 60 months. The median follow-up was 12,5 months. The group that responded to treatment, including stabilization, achieved a 1-year Kaplan-Meier overall survival rate of 72% and a 2-year rate of 45,6%. In patients with continued growth of lesions, the 1-year overall survival rate according to the Kaplan-Meier method was 42,6%, and the 2-year survival rate was not achieved. 48 patients were alive at the time of the study, 24 died from disease progression.

Conclusions: the use of TACE in metastatic lesions of the liver by choroidal melanoma in combined treatment or in mono-regimen led to an objective response or stabilization of the process in 73,6% of patients. This method increases the overall survival of patients and is well tolerated.

Keywords: choroidal melanoma, metastases, transarterial chemoembolization.

Detection of EGFR mutations in tumor tissue is the gold standard for prescribing tyrosine kinase inhibitor therapy.However even in the same molecularly defined population effect of the treatment, response duration and survival might differ significantly. We did a prospective clinical trial to assess ctDNA-based EGFR mutations as a prognostic marker for patients with lung adenocarcinoma receiving TKI as first-line treatment.

Materials and methods. A total of 122 patients with lung adenocarcinoma had EGFR mutations in tumor tissue. The determination of ctDNA was performed before the start of therapy. The determination of ctDNA after 2 months of the therapy was performed for 99 patients.

Results. In 32/99 samples taken before the start of TKI therapy and after 2 months of therapy, no ctDNA was detected(group 1). In 67/99 patients, ctDNA was detected before the start of drug therapy: in 42/67 (62,7%) ctDNA was not detected in blood after 2 months of therapy (group 2), in 25/67 (37,3%) patient ctDNA was detected in blood during therapy (group 3). Survival was significantly higher in the group with no ctDNA compared to the group where the ctDNA was determined before starting therapy (56,2 months vs 15,4 months, p<0,000).
The objective response was significantly higher in the 1st and 2nd groups compared to the 3rd group (50% and 66,7%
vs 28,0%, p=0,002). PFS was also higher in groups 1 and 2 compared to groups 3 (24,1 months and 19,0 months vs 10,3
months, p=0,003).

Conclusions. The absence of EGFR mutated ctDNA at baseline and clearance after 2 months of TKI therapy defines a
group with the best prognosis.

Keywords: mutations, EGFR, tumor, ctDNA, therapy.

The incidence and mortality from cervical cancer (CC) remains high. There are few effective options among chemotherapeutic agents for the treatment of recurrent and metastatic CC. One of the novel therapeutic approaches is to induce anti-cancer immunity by immune checkpoint inhibitors (ICI). The search for prognostic biomarkers to improve the efficacy of immunotherapy is ongoing. The efficacy and safety of ICI, either used as monotherapy or in combination with chemotherapy, radiation therapy, is being evaluated in several clinical studies. Early results are promising, making ICI an important field of research in the development of novel therapies for CC.

Keywords: cervical cancer, immunotherapy, immune checkpoint inhibitors, pd-1,

Overdiagnosis is the main «driver» of the growing epidemic of thyroid cancer in the world. More than half of cases of thyroid cancer in women are the result of overdiagnosis, i.e. diagnosis of a tumor, the probability of progression and metastasis of which is extremely low.

Our analysis showed that the incidence of thyroid cancer in Russia and most of its administrative regions is growing. At the same time, we observe pronounced interregional variability in the incidence rate. A very highage adjusted incidence rate, especially among women, is registered in the Bryansk region and other high-risk regions. The main cause of the increase in the incidence of thyroid cancer in the regions adjacent to the Chernobyl nuclear power plant is exposure to radioactive iodine (131I ) in childhood and adolescence. However, an increase in the incidence of thyroid cancer in this region at least partly is a consequence of ultrasonography (US) screening and the identification of clinically insignificant lesions. Only 40% of cases of thyroid cancer detected as a result, of screening could be the attributed to radiation. Accordingly, 60% are latent tumors that would never have clinically shown themselves if they had not been identified as a result, of screening.Altai region is also considered a high-risk region because it borders with the Semipalatinsk region of Kazakhstan the region where the former Soviet nuclear test site was located. Inthe Altai region, the introduction of US screening led to an increase in the detection of thyroid cancer from 8,7% in 1992 to 20,3% in 1999.

A marked increase in incidence in Russia, the increase in incidence in middle age and as a result the change in expected exponential pattern of age-specific curve into inverted «U», a very high incidence to mortality ratio, a very high cancer survival rate, which statistically significantly correlates with incidence, a statistically significant correlation between the proportion of tumors detected at the first stage and the incidence of thyroid cancer, a statistically significant correlation between prevalence of thyroid cancer and the incidence is a clear evidence of overdiagnosis. We estimate that the number of overdiagnosed thyroid cancer in Russia over 27 years ranges from 99000 to 138000 cases. We do not have sufficient retrospective data to estimate more accurately the size of thyroid cancer overdiagnosis in Russia. Thyroid cancer incidence data for Russia overall is available only from 1989.

Keywords: thyroid cancer, incidence, mortality, trends, latent cancer, non-invasive follicular neoplasia, ultrasound screening, survival, overdiagnosis

In this experimental study heart rate variability (HRV) using electrocardiography was studied in a small group of volunteers (10 people) who have never smoked (4), ex-smokers (4) and active smokers (2). Different nicotine delivery systems and smoking simulators, including regular, nicotine-free and electronic cigarettes, tobacco heating systems, chewing gums and a completely new product on the domestic market – nicotine packs of oral fixation (NPOF) were used. Supplemented with hormonal studies (stress hormones in saliva and catecholamines in the blood), HRV analysis showed relatively small changes in HRV with systemic use of packs with moderate nicotine content (up to 6 mg), which makes this type of product a leader in biological safety among the studied alternative delivery systems nicotine.

Keywords: nicotine, oral packs, heart rate variability, neurohormones.