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Malignant tumours

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Vol 10, No 1 (2020)
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DIAGNOSTICS AND TREATMENT OF TUMORS. CURRENT STATUS OF THE PROBLEM

5 ‑20 1202
Abstract

The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients.

Purpose: To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting.

Material and methods. We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated.

Results. The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors).

Conclusion. More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.

ORIGINAL ARTICLES, OWN RESEARCH

21‑28 6572
Abstract

One of the main issues in the treatment of multicentric breast cancer (BC) is to choose the type of surgery (paying attention to the tendency to reduce the volume of surgical interventions). Many studies have demonstrated an adverse effect of this form of BC on long‑term survival outcomes (increased risk of recurrence, decreased overall survival rates, etc.). However, none of the studies examined the effect of surgery extent on the quality of life of these patients.

Objective. To assess the effect of the surgery type on the quality of life of patients with multicentric BC.

Materials and methods. 190 patients were included in the study. The median follow‑up was 72 (7–116) months. Age ranged from 27 to 76 years. The majority of patients (150 women, 78.9 %) had luminal HER2‑negative tumors, while «aggressive» (HER2‑overexpressing, triple negative) subtypes were detected in 40 (21.1 %) of them. 134 patients underwent radical mastectomy (40 of which also had immediate breast reconstruction), 56 received breast‑conserving surgery. Statistically significant differences were not observed among stages III and I–II BC (p = 0.125). The quality of life was assessed with the use of EORTC QLQ-C30 and EORTC QLQ-BR23 scales at ≥ 12 months after performing surgical treatment.

Results. The quality of life was assessed depending on the type of surgical intervention. The patients after breastconserving surgery and immediate breast reconstruction demonstrated a significant advantage, primarily in the general perception of one's own health (p < 0.05) and emotional status (p < 0.05). Also, there were no significant differences in quality of life between the groups of patients after breast‑ conserving surgery and immediate breast reconstruction.

Conclusion. Due to the increase in the life expectancy of breast cancer patients, the issues of maintaining a high quality of life are becoming increasingly important. From this point of view, performing breast‑ conserving and reconstructive surgeries is preferable for patients with multicentric BC.

29‑34 656
Abstract
Introduction. Gastric cancer remains the leading cause of death from malignant neoplasms. Its pathogenesis is known to be a multistage and heterogeneous process with a wide range of genetic changes. Among the leading mechanisms, the dysregulation of the most important signaling cell pathways is distinguished, which determines the disruption of the cell cycle, cell differentiation, DNA repair, and apoptosis processes and leads to the development of gastric cancer. This work aimed to study the expression of the AKT/mTOR and AMPK signaling pathway components after the FLOT chemotherapy in patients with gastric cancer.

Material and methods
. The study includes 24 patients with gastric cancer. The patients received combined treatment, including neoadjuvant chemotherapy (FLOT) and surgical resection of the stomach. Specimen contained normal and tumor tissues obtained during diagnostic gastroscopy of patients. The mRNA level of the studied parameters was determined by real‑time PCR.

Results
. Significant changes occurred when examining the level of indicators after treatment. Against the background of non‑adjuvant therapy, there was a decrease in 4EBP1 expression by 2.2 times compared to its level before surgery.

The effect of the treatment was associated with a set of indicators
. They allow predicting the impact of therapy. There was a decrease in the expression of 4EBP, mTOR, and AMPK as the effect of treatment decreased in groups of patients with complete regression, partial regression, stabilization and progression of the disease.

Conclusion
. A decrease in 4EBP1 expression was found in gastric cancer tissue under the influence of neoadjuvant therapy. Molecular markers that can predict the development of resistance to antitumor therapy are associated with the features of the AKT/mTOR signaling pathway. The initially high expression of AMPK, mTOR, and 4EBP1 is a key event mediating the development of the neoadjuvant therapy effect in gastric cancer.

CLINICAL NOTES

35-40 1481
Abstract
Primary gastric melanoma is an extremely rare disease. Melanoma of upper gastrointestinal tract usually occurs as metastasis from a primary skin tumor in 1 to 4 % of cases. The paper describes a case report of primary gastric melanoma in a female patient who received complex therapy at the State Healthcare Institution Ulyanovsk Regional Clinical Oncology Dispensary.
41-48 1053
Abstract
Lynch syndrome (LS) resulting from the abnormal repair of unpaired DNA bases is characterized by an increased risk of colorectal, endometrial, and urinary tract cancers. Regardless of the tumor type, immunotherapy with immune checkpoint inhibitors (ICIs) has been approved for the treatment of patients with unresectable or metastatic DNA mismatch repair‑ deficient (dMMR) tumors, which may present a treatment option for patients with LS. The article contains a case report of a female patient with a germline MLH1 mutation and multiple primary colonic malignancies treated with nivolumab for 26 months. This observation demonstrates the success of immunotherapy after 6 lines of chemotherapy, implying potential control of tumor growth in patients with LS.
49-53 757
Abstract
The article presents a rare case report about the use of thoracoscopic transdiaphragmatic approach to resection of a solitary segment VIII metastasis in the liver (1.5 × 1.2 cm). Taking into account the difficulty of laparoscopic resection of postero ‑superior segments of the liver, a decision was made to refrain from laparotomy and to perform a safe minimally invasive surgery using an approach, which is rare at the current stage. The article also presents the analysis of published literature and discussion of a non‑ standard approach in this clinical case.


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ISSN 2224-5057 (Print)
ISSN 2587-6813 (Online)