№81. Перспективные мишени в лечении злокачественных опухолей
- E.N. ImyanitovDOI 10.31917/2004261
Molecular genetic analysis is a mandatory component of modern clinical oncology. The best developed area of application of DNA testing is related to the management of patients with hereditary cancer syndromes. Administration of a number of targeted drugs relies on the identification of somatic mutations in tumor tissue. There is a growing interest to so-called liquid biopsy, which is aimed at identification of tumorspecific fragments (DNA, RNA, proteins, cells etc.) in peripheral blood or other body fluids. Individual generation of tumor cell lines and xenografts is an attractive component of personalized cancer medicine. Incorporation of next generation sequencing in the management of cancer patients appears to be key event of this decade, which will significantly reshape daily medical practice in the near future.
Keywords: molecular genetic analysis, oncology, DNA test, diagnostics, targeted drugs, tumor, new generation sequencing.
- S.A. TyulyandinDOI 10.31917/2004274
During the last twenty years the identification of oncogenic driver mutations has enabled the development of targeted therapies that specifically inhibit mutationinduced pathways and showed unprecedented clinical response compared with conventional chemotherapy. Patients with disseminated non-small cell lung cancer, melanoma, GIST and etc. harboring the genetic alterations are demonstrated a dramatic tumor response and longer overall survival. Tumor genetic testing or liquid biopsy has become a routine procedure in the clinic. Several factors are limited the efficacy of targeted therapy, including the small proportion of patients with
actionable alterations, the complex heterogeneity and rapid evolution of tumors, which call for multitargeted therapeutic
approaches that are likely to be highly toxic, and finally limited availability of such targeted agents. Both success and failures
of the targeted therapy is a beginning of the long road to precision oncology. Here we review current implementations of
targeted therapy in clinical practice and highlight the achievements and limitation of biomarker-driven approach.
Keywords: targeted therapy, oncology, cancer, melanoma, tumor evolution.
- V.A. Chubenko, L.A. Zagorskaya, V.S. Chubenko, F.V. Moiseenko, N.Kh. Abduloeva, A.S. Zhabina, M.M. Kramchaninov, K.V. Shelekhova, A.A. Meldo, E.M. Zykov, A.A. Kudryavcev, E.V. Napolskaya, V.M. MoiseyenkoDOI 10.31917/2004289
One of the strategies to overcome the resistance to modern drug treatment is the metronomic therapy of the malignant tumors. This is a chronic continuous administration of low doses of the drugs in order to influence both tumor cells and their microenvironment in order to change the natural history of the growth of the malignant tumors and increase the overall survival. The aim was to study the effectiveness of the metronomic regimen of cyclophosphamide and methotrexate in patients with various malignant tumors.
Materials and methods. The experience of the metronomic chemotherapy with cyclophosphamide and methotrexate over 3,5 years in the Oncology Center is analyzed. Of the 678 patients, the vast majority (377) were patients of the older age group. 343 patients were in a poor condition (ECOG 2-4). MT was prescribed in various lines of the treatment, but mainly, after the development of resistance to the standard treatment (from the 2nd and more). The diagnosis were extremely
heterogeneous (colon cancer – 103, breast cancer – 84, head and neck tumors – 80, lung cancer – 78 and primary multiple tumors – 72). Number of metastatic sites were 2 and more organs. Adenocarcinoma and squamous cell carcinoma were more often.
Results. The objective response was 8,1%. Stable disease was 68,9%. Progressive disease was reported in 23% of cases. The median time to progression was 7 months. The metronomic therapy regimen was well tolerated and had no any clinically significant toxicity.
Conclusions. The work demonstrates the clinical effectiveness of the metronomic regimen of cyclophosphamide and
methotrexate in various malignant neoplasms.
Keywords: metronomic chemotherapy, stable disease, time to progression, toxicity.
- A.S. Tyulyandina, V.М. Nechushkina, L.V. Cherkes, K.Y. Morkhov, A.A. Rumyantsev, I.A. Pokataev, E.V. Glazkova, E.R. Virshke, D.Y. Frantsev, K.I. Zhordania, Y.V. Bujdenok, R.K. Valiev, A.V. Petrovsky, Y.S. Sergeev, I.V. Panichenko, A.A. Bulanov, M.B. Stenina, S.A. TyulyandinDOI 10.31917/2004299
Background: despite the fact that intraperitoneal (IP) chemotherapy in patients (pts) with ovarian cancer (OC) in 1 line of treatment showed positive results in three randomized studies, this method is still not routine in clinical practice.
Materials and methods: phase 2 study of the first line IP chemotherapy in pts with OC stage Ic – IV after primary optimal debulking was conducted. IP ports were implanted intraoperatively or by laparoscopic approach. Pts were administered every 3 weeks intravenous (IV) paclitaxel 135 mg/m2 day 1, IP cisplatin 75 mg/m2 day 2 and IP paclitaxel 60 mg/
m2 day 8 for 6 cycles.
Results: from 2009 to 2017 64 pts were included in the study. Progression free survival (PFS) was 38,6 months, overall survival (OS) was 79,4 months. In 79,7% of cases, the pts received all planned treatment. In retrospective comparison with similar group of pts who received standard IV chemotherapy in 2007–2017 no any significant difference were found in PFS and OS. A comparative analysis of pts with complete cytoreduction demonstrated significant increase in PFS of 11,7 months after IP chemotherapy than standard IV administration: 38,8 months for IP and 26,9 months for IV (HR 0,53; 95% CI 0,27–0,96; р=0,05). The same trend was observed for pts with stage III–IV: PFS for IP group was 38,6 months and for IV – 22,9 months (HR 0,60; 95% CI 0,36–0,98; p=0,05).
Conclusion: studied IP regimen of chemotherapy is tolerable for majority of pts. The use of IP chemotherapy in first
line OC may be an option in pts with minimal residual tumor after primary cytoreduction.
Keywords: ovarian cancer, intraperitoneal chemotherapy, intravenous chemotherapy, optimal cytoreduction, cisplatin, paclitaxel.
- N.E. Levchenko, E.A. Efremov, E.V. Kasatonova, Yu.S. Sidorenko, Y.I. Melnik, A.V. KoryakinDOI 10.31917/2004310
Primary gonadal insufficiency is a recognized late effect in patients with an oncological history. Hormone deficiency affects the quality of life, cardiometabolic and psychological health with a further increase in morbidity and mortality, increases the risks of sexual dysfunction and infertility. The expansion of the indications for hormone replacement therapy (HRT) is a point to be discussed. Most of the existing clinical guidelines contain chapters on HRT, however, it is not clearin the context of young women with premature ovarian failure or men with testicular insufficiency due to cancer or its treatment. In this review we tried to systematize the available data for the most common oncological diseases, depending on the possibilities of using HRT for men and women.
Keywords: cancer survivor, estrogen replacement, testosterone replacement, HRT, hormone replacement therapy, MHT, menopausal hormone therapy, recurrence risk.
Dynamics of pathological factors after «test» course of preoperative endocrine therapy in menopausal patients with earlyer positive breast cancer and its effect on survivalM.A. Frolova, M.B.Stenina, Y.I. Kochetkova, A.V. Petrovsky, O.V. Krohina, Y.V. Vishnevskaya, S.A. TyulyandinDOI 10.31917/2004326
Background: the choice of adjuvant therapy in early ER positive Her2 negative breast cancer (BC) is difficult due to significant heterogeneity of these tumors. Additional instruments are needed to help in identifying the right tactics.
Goal: to research the Ki67 dynamics after the short «test» course of preoperative endocrine therapy and to evaluate its
impact on survival.
Materials and Methods: 100 postmenopausal patients (pts) with early stage (T1-2N0-1M0) ER positive Her2 negative BC were included in the study. They received the short (2–3 weeks) course of preoperative endocrine therapy with tamoxifen or aromatase inhibitors. Postoperative pathology report included repeated evaluation of Ki67, ER, PR, TILs.
Results: after the short course of endocrine therapy there was a significant decrease in Ki67 (p=0,001) and PR expression (p=0,001), ER expression did not change. Only the preoperative level of Ki67 impact its decrease to the goal evel of <10%. With the baseline level of 10–30% its decrease to the goal level was observed in 56% cases, while with baseline level >30% – in only 21%. The baseline level of Ki67 did not impact the survival in opposite to postoperative level. 5-year DFS was 100% with Ki67 <10%, 97,4% – with Ki67 10–30% and 76,4% – with Ki67 >30% (р=0,02).
Conclusion: the level of Ki67 <10% after the short course of preoperative endocrine therapy, was associated with excellent survival rates in postmenopausal pts and allows to consider omitting of chemotherapy and thus safely de-escalate adjuvant therapy.
Keywords: ER positive breast cancer, preoperative endocrine therapy, Ki67.
Long-lasting full remission after selective intra-arterial chemotherapy for recurrence of locally advanced oral mucosa carcinomaI.P. Moshurov, A.N. Redkin, N.A. Znatkova, M.S. Olshansky, A.Yu. Shklyarov, A.V. Tsurikova, S.A. StikinaDOI 10.31917/2004336
Objective: To present the effectiveness of selective intra-arterial chemotherapy and chemoembolization for management of head and neck squamous cell carcinomas recurrence and long-lasting remission.
Material and methods: Patient 27 years old, with histologically verified squamous cell carcinoma of the oral mucosa
of III T2N1M0 had been treated by chemoradiation. Two courses of intravenous (IV) Cisplatin a dose of 100 mg/m2 were
performed and 3-D conformed radiotherapy by 2 Gy fractions x 1 time a day to a total dose of 40 Gy. Interruption of the
treatment was due to the development of radiation mucositis. After 2 additional courses of IV cisplatin 100 mg/m2 and
achievement of total radiation dose 70 Gy was marked the relapse. To eliminate growing residual tumor intra-arterial (IA)
chemotherapy and selective chemoembolization were applied.
Results: A reduction of the tumor size was marked soon after the first course of IA chemotherapy (Cisplatin 150 mg and
5-fluorourocyl 1000 mg) and embolization of the thyroid arterial branch with PVA particles. Cicatricial changes in the oral
cavity were noted after the second course of IA chemotherapy. After the fifth course of IA chemotherapy and consequential
chemoembolization of facial artery the tumor was eliminated and full remission was obtained. The relapse was not revealed
in follow up observation during 4 years. The objective result was confirmed by PET-CT.
Conclusion: The original technique of selective intra-arterial chemotherapy and chemoembolization combination is
an effective approach for residual squamous-cell head and neck carcinomas management after completed chemoradiation.
This approach could be a last-chose method to obtain long-lasting remission.
Keywords: squamous cell carcinoma of the head and neck, relapse of oral cavity cancer, chemoradiation, intra-arterial chemotherapy, chemoembolization.
- S.S. Artemiev, Z.A.-G. Radzhabova, R.A. Nazhmudinov, M.A. Kotov, E.V. Artemieva, M.A. RadzhabovaDOI 10.31917/2004343
This article presents a method for performing puncture cryodestruction of a tumor оf oropharyngeal area, and possible
complications after this procedure. In this paper, we analyzed the treatment of patients with oral squamous cell carcinoma.
The study showed that the use of new domestic equipment allows to introduce into practice a method of surgical treatment
of patients with locally advanced cancer of the tongue and oropharyngeal area. It allows radical surgery on the patient
with preservation of the functions of the oral organs without significant functional losses.
Keywords: cooling, cryosurgery, freezing, oral tumors.