Vol 23, No 2 (2021)

CLINICAL ONCOLOGY

Prostate cancer

Kaprin A.D., Alekseev B.I., Matveev V.B., Pushkar’ D.I., Govorov A.V., Gorban’ N.A., Kirichek A.A., Biriukov V.A., Volkova M.I., Gulidov I.A., Gumenetskaia I.V., Krylov V.V., Kariakin O.B., Krasheninnikov A.A., Mardynskii I.S., Niushko K.M., Zakharova T.I., Kostin A.A., Khmelevskii E.V., Fedenko A.A., Bolotina L.V., Falaleeva N.A., Filonenko E.V., Nevol’skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G.

Abstract

Prostate cancer (RPP) is a malignant neoplasm that arises from the epithelium of the prostate gland gland (PJ).

Thethiology and pathogenesis of this disease remain poorly studied. Many studies are aimed at studying diet, food, hormonal impact, as well as infections in the etiology of the RLPG. The prevalence of RPL depends on ethnic and geographical features. The highest incidence of African Americans living in the United States (60% higher than that of white Americans), the least high - in the Chinese living in China [1]. In addition to racial features, the risk factors of the RPG are considering the genetic predisposition, the age of men and nutritional features. The probability of developing a PJ tumor in a man who has one of the closest relatives of the first degree of kinship (father or brother) sick of the RLPG, is 1.8 times higher than in the population. If two relatives were sick or more (father and brother or both brothers), the risk of RPG increases in 5.51 and 7.71 times, respectively [2, 3]. African Americans have an increased risk of identifying RPG, as well as a greater probability of detecting aggressive RPG [4]. Also, the risk of RLPG is rising in men who use a large amount of animal fats [5].

Journal of Modern Oncology. 2021;23(2):211-247
pages 211-247 views

The use of erythropoietins in oncology

Abstract

The editorial article presents information about the problem of the use of erythropoietins in anemia in cancer patients in conjunction with the results of Cochrane systematic reviews – the «gold standard» of the quality of evidence-based medical information.

Journal of Modern Oncology. 2021;23(2):248-250
pages 248-250 views

Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer (Russian Translation of Cochrane Plain Language Summary – PLS)

Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Lambin P, Ramaekers BLT, van Mastrigt GAPG, Van den Ende P, de Jong J, De Ruysscher DKM, Pijls-Johannesma M. Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006158. DOI: 10.1002/14651858.CD006158.pub2

Journal of Modern Oncology. 2021;23(2):250-250
pages 250-250 views

Anti-anemia drugs shorten survival for some cancer patients (Russian Translation of Cochrane Plain Language Summary – PLS)

Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke MJ, Weingart O, Kluge S, Piper M, Napoli M, Rades D, Steensma D, Djulbegovic B, Fey MF, Ray-Coquard I, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A. Erythropoietin or Darbepoetin for patients with cancer – meta-analysis based on individual patient data. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007303. DOI: 10.1002/14651858.CD007303.pub2

Journal of Modern Oncology. 2021;23(2):251-251
pages 251-251 views

Erythropoietin or darbepoetin for patients with cancer (Russian Translation of Cochrane Plain Language Summary – PLS)

Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Tonia T, Mettler A, Robert N, Schwarzer G, Seidenfeld J, Weingart O, Hyde C, Engert A, Bohlius J. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD003407. DOI: 10.1002/14651858.CD003407.pub5

Journal of Modern Oncology. 2021;23(2):252-252
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The Russian Expert Council on the application of new highly selective inhibitor of Bruton’s tyrosine kinase zanubrutinib in the treatment of patients with relapsed/refractory mantle cell lymphoma. Event review

Kaplanov K.D.

Abstract

The meeting of the expert council concerning the application of new highly selective inhibitor of Bruton’s tyrosine kinase zanubrutinib in the treatment of patients with relapsed/refractory mantle cell lymphoma was held in Moscow on April 21, 2021. The leading Russian experts in the field of oncohematology took part in the meeting.

Journal of Modern Oncology. 2021;23(2):253-255
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Refractory metastatic colorectal cancer: challenges and solutions during the COVID-19 pandemic

Sekacheva M.I., Fatyanova A.S., Meretukov D.A., Zhilenkova A.V., Rusanov A.S., Rozhkov A.A., Guryanova A.A., Bagmet N.N.

Abstract

Colorectal cancer (CRC) is one of the leading cancers in terms of prevalence and mortality. Almost 1/4 of patients with CRC have metastases at the initial presentation. The survival rate of this group of patients remains low. With the onset of the COVID-19 pandemic, cancer patients have faced difficulties in getting diagnosis or treatment, which could potentially lead to an increase in late-stage tumors and mortality. This situation required changes in approaches to the treatment of cancer patients, such as replacing drugs with tablet forms, schemes with long intervals, and much more. It is known that about 50% of patients with metastatic colorectal cancer survive in satisfactory condition until the 3rd line drug therapy or longer. One of the main drugs for this category of patients is regorafenib, which, thanks to the tablet formulation, has become especially important in the COVID-19 pandemic. In numerous clinical studies, the drug showed an increase in patient overall survival and good safety profile. In addition, there is growing evidence of the effect of regorafenib on tumor sensitivity to treatment with platinum drugs, irinotecan, and EGFR inhibitors.

Journal of Modern Oncology. 2021;23(2):256-259
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Experience of the department of surgical treatment of bone and soft tissue tumors during COVID-19 pandemic period

Bukharov A.V., Derzhavin V.A., Yadrina A.V., Erin D.A.

Abstract

Since December 2019 the new coronavirus disease (COVID-19) has hit the world, causing the World Health Organization to declare it a pandemic. With the emergence and spread of the new infection, there has been unprecedented pressure on health care systems around the world. The time constraints associated with receiving routine care also affected the risk group – cancer patients, as some hospitals were quarantined. Violation of the terms of both systemic drug, radiation and surgical treatment of cancer patients could lead to the progression of the tumor process and lead to the death of the patient. In connection with the current situation, doctors had to quickly change the tactics of managing cancer patients, due to the lack of accurate data on the basis of which it is possible to determine the optimal approach to the use of therapy, they had to make decisions in conditions of lack of data. The article shows an example of the treatment of 113 patients being treated in the department of surgical treatment of bone and soft tissue tumors in National Medical Research Radiological Center of the Ministry of Health of Russia during the first wave of the pandemic from March 30 to July 1, 2020. Surgical treatment was performed in 103 patients. During the period of stay in the hospital, 11 patients showed signs of coronavirus infection. Of these, 10 patients were diagnosed with coronavirus infection in the postoperative period. According to the study, the nosocomial incidence of COVID-19 is 10%. With timely diagnosis and specialized treatment, the survival rate was 100% in the given example. Consequently, if epidemiological measures are observed at all stages of hospitalization, it is possible to carry out planned surgical treatment for patients with primary and secondary lesions of bones and soft tissues. However, the decision to carry out a planned operation during a pandemic should be individual for each patient.

Journal of Modern Oncology. 2021;23(2):260-262
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Biological features of ductal carcinoma in situ: clinical role and basis for treatment individualization

Kolyadina I.V., Butrimova A.S., Poddubnaya I.V., Kоmetova V.V., Rodionov V.V.

Abstract

Ductal carcinoma in situ (DCIS) is an extremely heterogeneous disease in terms of clinical manifestations, morphological changes, and expression of biomarkers, which determine the risk of subsequent development of an invasive breast cancer (BC). Diagnosis and treatment of DCIS prevents the development of invasive tumors (which reduces the potential risk of death from BC); however, the prognostic value of local treatment depends on the biological characteristics of its. The tumor grade, presence of comedonecrosis and expression of estrogen receptors are the key prognostic factors in DCIS for the treatment tactics and prognosis. The clinical symptoms of DCIS are very scarce, the most of tumors is diagnosed by screening mammography; the typical sign of DCIS is malignant microcalcifications or changes of breast architectonic. The sensitivity of mammography, ultrasound and MRI directly depend on the biological characteristics of DCIS. Surgical treatment (breast-conserving surgery or mastectomy) significantly reduces the risk of BC death in women with DCIS G2/G3, and radiotherapy after breast-conserving surgery reduce the risk of local recurrence of non-invasive and invasive BC. The choice of the local treatment (breast-conserving surgery ± radiation therapy vs mastectomy) depend on such factors as: tumor size, localization, clear margins, and biological characteristics of DCIS. In contrast to invasive cancers, the negative margin in DCIS is more than 2 mm from the tumor. Regional lymph node involvement in DCIS occurs in less than 1% of cases; however, microinvasion is found in analyze the surgical specimen in 15% of patients, which raises the question about regional staging. Risk factors for microinvasion in DCIS are age less than 55 years, tumor lesion size more than 4.0 cm, DCIS grade G3, and tumor palpability. Adjuvant endocrine therapy with tamoxifen significantly reduces the 10-year risk of invasive recurrence by 51%, the risk of contralateral BC by 50% and the risk of death by 40%, but only for hormone-positive DCIS. HER2 overexpression is found in DCIS significantly often (up to 40% of cases) than in invasive BC, HER2+ status correlates with DCIS high grade G3, the presence of comedonecrosis and with increased risk of relapse (both non-invasive and invasive) but is not a reason for anti-HER2 therapy. DCIS low risk and DCIS high risk have not only different morphological characteristics, but also different models of biological behavior, which must be considered in the different choice of treatment tactics.

Journal of Modern Oncology. 2021;23(2):263-268
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PIK3CA mutation: changing the paradigm of HR+ HER2-negative metastatic breast cancer therapy. Review of the Novartis Pharma satellite symposium, held as part of a virtual forum dedicated to the diagnosis and treatment of patients with hormone-dependent HER2-negative advanced breast cancer with a PIK3CA gene mutation. April 23, 2021

Abstract

А virtual forum dedicated to the diagnosis and treatment of patients with hormone-dependent HER2-negative advanced breast cancer (HR+ HER2- aBC) with the PIK3CA mutation using target drug alpelisib was held on April 23, 2021. Oncologists from France and Russia discussed the significance of the PIK3CA mutation, the necessity and methods of its identification. They also shared information and exchanged experience of using alpelisib to treat patients who had previously received a CDK4/6 inhibitor and were resistant to endocrine therapy. Using the example of a clinical case, the experts also discussed the issues of prevention and correction of adverse events.

Journal of Modern Oncology. 2021;23(2):269-274
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Breast cancer immunophenotype and its relationship with haematopoiesis

Ryabchikov D.A., Chulkova S.V., Shamilov F.A., Chanturia N.V., Zheltikov S.D., Tupitsyn N.N.

Abstract

Background. The applying of immunotherapeutic approaches in cancer treatment requires a deep and comprehensive understanding of the tumor biological characteristics. In this regard, the study of the tumor immunophenotype is one of the leading scientific directions. The major histocompatibility complex molecules are considered to be the promising markers of the immunotherapy effectiveness prediciton.

Aim. To research tumor immunophenotype in different molecular subtypes of breast cancer (BC).

Materials and methods. The study included 99 patients with BC. Luminal cancer – 84.8% (n=83), Erb-B2 overexpressing (HER2+) subtype – 5.0% of cases (n=5), triple-negative BC – 10.2% (n=10). Stages: T1 (51.5%), T2 (44.4%), T3 (2.0%). Lymph node metastases (N+) were present in 39.4% (n=39) of cases. Grade of malignancy: 80.8% (G2). Samples of tumor tissue and bone marrow were examined. Immunophenotyping of the tumor was carried out on cryostat sections by the method of immunofluorescense. Antibodies to HLA-I, HLA-DR, CD71 were used and were directly conjugated to fluorochromes PE, FITC, PE-Cy5. The bone marrow was examined by a morphological method using light microscopy. Statistical data processing was performed using the IBM-SPSS statistics v2.1.

Results. In 50.8% (31/61) cases of luminal BC (LBC), the HLA-I molecule is absent on the membrane or is expressed by single tumor cells. A decrease in HLA-I expression levels in the luminal subtype was combined with the absence of HLA-DR antigens, which was found in 63.1% of cases. A higher frequency of HLA-I expression is observed in the Erb-B2 overexpressing BC, the differences are insignificant. Expression of CD71 was defected in 67.8% (40/59) of the studied samples of LBC. CD71 was expressed on the surface of most tumor cells (70%) in triple-negative BC. There were no statistically significant differences between the studied molecular subtypes of BC. Analysis of the luminal subtypes revealed that CD71 expression was observed much more often in luminal B subtype: 76.5% (n=26) and 75% (n=3) versus 52.4% (n=11). HLA-I expressing luminal cancer were characterized by higher levels of erythroid precursors (polychromatophilic normoblasts 9.0±0.9 and 5.8±0.8%, p=0.0017; oxyphilic normoblasts (7.9±0.7 and 5.3±0.6%, p=0.008), an increase in the amount of erythroid germ cells (17.7±1.5 and 11.6±1.5%, р=0.009) and an increased content of myelokaryocytes (93.1±17.1 thousand/µl versus 57.3±9.0 thousand/µl, p=0.083).

Conclusion. In LBC a decrease in the expression levels of HLA-I class molecules was noted in combination with the absence of HLA-DR antigens on the membrane of tumor cells, which was observed in more than half of the analyzed samples. The frequency of expression in triple-negative cancer is higher than in the luminal subtype. There were no statistically significant differences between molecular subtypes by the level of expression of HLA-I and II class molecules. Transferrin receptor expression has been reported in most cases of triple-negative BC subtype. The interconnection between the expression of HLA-I histocompatibility molecules and hematopoetic parameters in LBC has been established.

Journal of Modern Oncology. 2021;23(2):275-279
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Synchronous thyroid gland metastases from breast cancer. Case reports

Ognerubov N.A., Antipova T.S., Palkina E.E.

Abstract

Background. Breast cancer is the leading cause of death in women. Distant metastases in different organs, including the thyroid gland, are still an urgent problem. Distant metastases are very rare in clinical practice. Nevertheless, the accumulated clinical and surgical experience in treatment has shown that breast cancer is the second most common primary tumor, leading to thyroid gland metastases, after kidney cancer.

Aim. Present the clinical observations of synchronous thyroid gland metastases from breast cancer.

Materials and methods. We observed two patients, aged 55 and 72 years, suffering from metastatic breast cancer with simultaneous metastases to the thyroid gland, to the cervical and mediastinal lymph nodes, to the lungs, to the ovaries and to the bones.

Results. A 55-year-old woman with a left sided neck mass and hoarseness has been suffering from the metastatic breast cancer with simultaneous metastases to the thyroid gland, to the cervical lymph nodes, to the lungs, to the ovaries and to the bones. The biopsy of the primary tumor has been performed. The tumor has the structure of invasive ductal carcinoma, G2, luminal A subtype, HER2-negative type in histological and immunohistochemical analysis. The spread of the tumor has been determined by positron emission tomography/computed tomography (PET/CT). Metastases from breast cancer have been cytologically proven during thin needle biopsy. A 72-year-old woman with a mass in the region of thyroid gland has been suffering from breast cancer with metastases to the thyroid gland, to the mediastinal and cervical lymph nodes, to the bones, and to determine this process PET/CT, the thyroid fine needle aspiration biopsy and core biopsy of primary tumor have been applied. The histological variant was represented by invasive ductal cancer, G2, luminal A subtype, HER-2 negative type. Taking into account the spread of the process, the patients were given polychemotherapy, targeted therapy and hormone therapy. There is no disease progression for 6 months.

Conclusion. Synchronous thyroid gland metastases in case of primary breast tumors are rare. In such cases, PET/CT is the important diagnostic method. The main therapeutic option in this case is systemic therapy, including chemotherapy, targeted and hormone therapy, the nature of the agent depends on the biological variant of the tumor.

Journal of Modern Oncology. 2021;23(2):280-286
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Modern possibilities of immunotherapy in the treatment of extensive-stage small cell lung cancer: experience of durvalumab application. Case report

Zhabina A.S., Moiseenko F.V., Volkov N.M., Abduloeva N.K., Moiseenko V.M.

Abstract

Extensive-stage small cell lung cancer (ES-SCLC) is characterized by an aggressive course, a high recurrence rate and fast progression. For a long time, the survival prognosis for the most patients suffering from this disease remained unfavorable. The situation changed with the appearance of chemoimmunotherapy in clinical practice. Chemotherapy based on durvalumab in comparison with the standard chemotherapy demonstrated the statistically and clinically significant increase in median overall survival in patients with previously untreated ES-SCLC in the CASPIAN international trial. This article deals with the case of the application of standard chemotherapy in combination with durvalumab as a first-line ES-SCLC therapy. The patient started receiving durvalumab therapy in June 2017 as a part of the CASPIAN international trial. In March 2021 the duration of therapy was 45 months, the patient had a complete regression of the disease.

Journal of Modern Oncology. 2021;23(2):287-291
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The use of atezolizumab in combination with chemotherapy in first-line of metastatic small cell lung cancer. Case report

Ognerubov N.A., Antipova T.S.

Abstract

Background. Lung cancer (LC) occupies a leading position among malignant tumors in the world, it accounts for 11.4% of the total malignant neoplasms. In 2020, there were 2 206 771 new cases of LC and 1 796 144 deaths worldwide. Among the histological variants, small cell LC (SCLC) has the most unfavorable outcomes. This variant is considered highly sensitive to chemotherapy. Despite some successes in the treatment of this disease, the results of treatment remain problematical. In recent years, the use of immune checkpoint inhibitors has provided significant control of the course of the disease.

Aim. To show the efficacy of atezolizumab in combination with chemotherapy in patients with metastatic SCLC.

Materials and methods. A 76-year-old patient with left lung cancer, IVA T4N3M1b, the right supraclavicular lymph node metastases, exudative pleuritis of the left lung was under observation. The histological investigation showed SCLC. Brain metastases were not detected. ECOG 0.

Results. The patient was treated using atezolizumab 1200 mg in combination with carboplatin 5 AUC and etoposide 100 mg/m2 on days 1, 2, 3 for four cycles, followed by a maintenance therapy regimen with atezolizumab 1200 mg every 21 days. The patient received 21 injections during 14 months. The assessment of treatment effect was evaluated using combined 18F-fluorodeoxyglucose positron emission and X-ray computed tomography. As a result of the treatment, after 7 months, a complete clinical and morpho-metabolic regression of the tumor was reached, which persisted throughout the period of the treatment. Among the adverse events were detected grade 2 anemia and first-stage sensory neuropathy. No immune-related adverse events were observed.

Conclusion. The addition of atezolizumab to etoposide + carboplatin as the first-line therapy for extensive-stage SCLC provides the long-term overall and disease-free survival with achieving the satisfactory quality of life in patients and acceptable drug tolerance.

Journal of Modern Oncology. 2021;23(2):292-298
pages 292-298 views

Outcomes of neoadjuvant chemotherapy in resectable, borderline resectable and locally advanced pancreatic cancer

Dalgatov K.D., Semenov N.N., Kozodaeva M.V.

Abstract

Background. The problem of neoadjuvant treatment of locally advanced (LA), borderline resectable (BR) and resectable pancreatic cancer (RPC) is being actively discussed at the present time, although the indications for its use have not been fully determined. In our work, we want to discuss the outcomes of using neoadjuvant chemotherapy (NACT) in these patients.

Materials and methods. From 2016 to 2020, 85 patients with pancreatic cancer were observed in the clinic (37 patients with LA cancer of the pancreas; 15 with BR cancer of the pancreas and 33 with RPC). Of these, men – 33 (38.8%), women – 52 (61.2%). The average age was 64 (31–83) years. All groups had GEMOX (41.2%) and FOLFIRINOX (58.8%) regimens. Increased CA 19-9 above normal had, in the LA group – 21 (56.6%); in the BR group – 9 (60%); and in the resectable group 26 (78.8%). From 3 to 6 courses of NACT were carried out, followed by computer tomography control and decision-making on treatment tactics.

Results. In the LA group, the GEMOX (n=15) and FOLFIRINOX (n=22) modes were used. When evaluating the results after 1 follow-up examination after 2.5 months. found: 2 patients died; progression – 14 patients (37.8%); remained inoperable – 16 patients (43.2%), of whom 9 received radiation therapy. Removal of the primary tumor was performed in 5 patients (13.9%). The average OS in this group was 15 months. Fifteen patients with BR pancreatic tumors were observed. NACT was carried out with the same regimens – GEMOX (n=7) and FOLFIRINOX (n=8) – for 2.5 months. When evaluating the results after 1 follow-up examination after 2.5 months was found: 1 (7.7%) patient died; progression was noted in 6 (40%) patients; in 1 (7.7%) patient, surgical treatment was not performed due to pronounced concomitant diseases. Surgical treatment was performed in 7 (46.7%) patients. 33 patients were prescribed NACT for RPC. The main criteria for prescribing NACT for formally resectable pancreatic cancer were a high CA 19-9 level (>100 IU/ml) [n=26 (75%)] and a large primary tumor [n=7 (25%)]. All patients received the same regimens for 3.3 months. up to 1 control. When evaluating the results, the following results were obtained: 1 (3%) patient died; 3 (9.3%) patients were not operated on due to refusal from surgical treatment; 7 patients (21.9%) were not operated on due to progression. Surgical treatment was performed in 22 (66.7%) patients; Whipple procedure in 17 patients, distal resection in 3 patients, total pancreatoduodenectomy in 2 patients. At the same time, complete morphological responce was noted in 2 (9%) patients, R0 resection in 19 (86%) patients, R1 – in 1 patient (4.5%). The median survival rate of the operated patients was 20.2 months (CI 13.2–27.2 months). Most patients (65.9%) had a high level of CA 19-9, which was studied in dynamics and used as a marker of the biological activity of the tumor.

Conclusion. Thus, we can claim that NACT is absolutely indicated for all patients with LA and BR pancreatic cancer, and its role in the selection of the most favorable in relation to the prognosis of patients is indisputable. Perioperative chemotherapy in patients with RPC is still controversial; however, having in mind the results in groups with LA and BR pancreatic cancer and the literature data, we dare to assume that for this issue it is a matter of time and future randomized trials. And here an important role can be played by the CA 19-9 level, which characterizes a biologically aggressive tumor, but again, prospective randomized studies are required to study this issue in more detail.

Journal of Modern Oncology. 2021;23(2):300-306
pages 300-306 views

The identification of tumor-infiltrating lymphocytes in patients with stomach cancer

Khakimova G.G., Bozhchenko Y.A., Zabotina T.N., Tryakin A.A.

Abstract

Background. Stomach cancer (SC) is the 6th most common neoplasm among cancers (1 033 701 cases; 5.7%) and the 3rd most deadly cancer worldwide for men and women (782 685 deaths, 8.2%). SC therapy is a complex treatment associated with surgery, adjuvant chemotherapy, targeted therapy and immunotherapy with checkpoint inhibitors, nowadays. Despite the fact that the SC understanding has significantly increased within recent years, the prognosis still remains poor. In addition, very often the patients with the same stage of SC according to the international TNM classification of malignant tumors have different overall survival. Therefore, in order to improve survival rates, is necessary to understand the mechanisms of disease progression and to find new effective predictive factors. Besides many SC predictive factors, such as clinical and morphological characteristics (Lauren histologic type of tumor, degree of differentiation), biomarkers, deficient mismatch repair (dMMR), we have also revealed the positive correlation between the degree of tumor infiltration of tumor-infiltrating lymphocytes (TILs), especially with the spatial location of cell types (intratumoral or stromal cells), and the survival indicators of the patients with malignant neoplasms, recently. Moreover, TILs are the most significant predictive factors in patient survival rates than the TNM classification. At the same time, TILs predictive role in SC is still not clearly defined. Thus, the understanding of the degree of tumor infiltration of TILs depending on the spatial location would allow to determine the predictive significance, as well as to determine the direction of the immune reactions generating in patients with SC at the tissue level, depending on the risk and probability of progression.

Aim. To study the predictive significance of intratumoral and stromal CD4+TILs, CD8+TILs and CD4+/CD8+TILs in patients with gastric adenocarcinoma.

Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 patients with stages I–III, 20 patients with stage IV) received surgical/combined treatment or independent chemotherapy, respectively, at the Blokhin National Medical Research Center of Oncology. The histological material was carried out before the treatment. Intratumoral (iTILs) and stromal (sTILs) values of CD4+TILs, CD8+TILs, CD4/CD8+TILs and the predictive significance in respect of overall survival and progression-free survival (PFS) were studied.

Results. During the observation period (16.4±6.2 months) CD4+/CD8+iTILs were factors of poor prognosis concerning PFS in patients of the first group (p=0.035; odds ratio – OR 3.264, 95% confidence interval – CI). We also identified the statistically significant decrease in CD4+iTILs, CD8+iTILs, CD4+/CD8+iTILs and the absence of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs in patients with metastatic SC (р=0.0003; р=0.000004; р=0.00001).

Conclusion. The results show the positive predictive significance of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs. At the same time, the increase of CD4+/CD8+iTILs reduces the PFS in patients with early and locally advanced SC.

Journal of Modern Oncology. 2021;23(2):307-312
pages 307-312 views

Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

Fedorinov D.S., Geidarov R.N., Shashkov I.A., Mikhailovich V.M., Lyadova M.A., Pokataev I.A., Lyadov V.K.

Abstract

Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors.

Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population.

Materials and methods. For the period from October 2020 to April 2021, 56 patients (women – 29, men – 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.3±11.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach – in 19 patients, tumors of pancreas and biliary tract – in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant – 19 patients, neoadjuvant – 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fisher’s exact test.

Results. The average number of chemotherapy courses received was 4.2±2.6 (1–12). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes.

Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.

Journal of Modern Oncology. 2021;23(2):314-318
pages 314-318 views

Immune-mediated adverse events in immune checkpoint inhibitors therapy: literature review

Lyadova M.A., Lyadov V.K.

Abstract

Immune-mediated adverse events (imAEs) are complications of therapy with immune checkpoint inhibitors, which arise as a result of autoimmune inflammation. The article summarizes systemic (fatigue, fever), cutaneous (rash, itching), gastrointestinal (diarrhea, colitis, hepatitis, pancreatic dysfunction), endocrinological (hypothyroidism, hypophysitis, adrenal insufficiency, diabetes mellitus), pulmonary (pneumonitis, pleuritis), rheumatological (arthralgia), neurological (headache, sensory and motor disorders), renal (acute interstitial nephritis, lupus-like nephritis, granulomatous nephritis, diffuse interstitial nephritis and minimal change disease), hematological (anemia, cytopenia), cardiovascular (myocarditis) and ocular (conjunctivitis, episcleritis, ceratitis, blepharitis and uveitis) imAE. Pathogenetic mechanisms and treatment approaches (in accordance with toxicity grade and clinical recommendations) are discussed. Early symptom recognition, patient education and timely intervention are crucial for imAE correction.

Journal of Modern Oncology. 2021;23(2):319-326
pages 319-326 views

Isatuximab, a novel anti-CD38 monoclonal antibody in the treatment of multiple myeloma: efficacy and safety

Zatolochina K.E., Zyryanov S.K., Ushkalova E.A.

Abstract

The article discusses the place of CD38 antibodies in the treatment of multiple myeloma (MM). Special emphasis is put of isatuximab. In 2020, isatuximab in combination with pomalidomide and dexamethasone was approved in Russia for the treatment of adult patients with MM who have received at least two lines therapies, including lenalidomide and a proteasome inhibitor. The published data from studies of isatuximab, demonstrating its clinical efficacy and safety in combination with standard treatment regimens for recurrent/refractory MM, are discussed.

Journal of Modern Oncology. 2021;23(2):327-331
pages 327-331 views

Acalabrutinib in the treatment of chronic lymphocytic leukemia: a review of recent evidence

Petrenko A.A., Kislova M.I., Dmitrieva E.A., Nikitin E.A.

Abstract

Chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically with the recently developed drugs targeting the B-cell receptor (BCR) signalling pathway. Acalabrutinib, a second generation Bruton tyrosine kinase inhibitor, was approved in 2020 in Russia for the treatment of patients with CLL. Acalabrutinib was developed as a more selective Bruton tyrosine kinase inhibitor then ibrutinib. This drug is aimed at reducing the adverse events that limit the use of ibrutinib, such as atrial fibrillation and bleeding. Phase I/II multicenter studies have demonstrated the efficacy and safety of acalabrutinib monotherapy in untreated CLL patients and in patients with relapsed/refractory CLL and ibrutinib intolerance. Phase III trials, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy and a combination of acalabrutinib and obinutuzumab versus standard therapies and demonstrated improved efficacy and tolerability of acalabrutinib. A phase III trial comparing acalabrutinib and ibrutinib monotherapy (ELEVATE-RR) is ongoing. The results of this study along with real-life clinical data could determine the place of acalabrutinib in CLL treatment.

Journal of Modern Oncology. 2021;23(2):332-338
pages 332-338 views

Metastatic cervical cancer: clinical experience with pembrolizumab application. Case report

Protasova A.E., Strakh L.V., Lando E.I., Sidorkina E.V.

Abstract

Cervical cancer (CC) ranks fourth for cancer incidences in women after breast cancer, colorectal cancer and lung cancer. There is a steady increase in the incidence of invasive forms of CC in Russia. Over the past quarter of a century, the mortality rate of reproductive age group women with cervical cancer has increased by 2 times. The standard treatment options for cervical cancer progression were the regime of paclitaxel plus cisplatin (carboplatin). The addition of an antiangiogenic therapy (bevacizumab) to the standard chemotherapy regimen increases overall survival of only 4%. The response to other lines of chemotherapy does not exceed 10% after the therapy using the combination of paclitaxel + carboplatin + bevacizumab. The results of KEYNOTE-158 trial demonstrated objective responses in 91% of CC patients lasting for more than 6 months in case of application of pembrolizumab 200 mg every 3 weeks in cases of PD-L1 expression (CPS≥1) with acceptable toxicity. The presented clinical case of successful treatment using pembrolizumab in women with PD-L1 expression in metastatic CC has a beneficial effect on further accumulation of experience and could help to choose the right treatment options in order to increase the efficacy of the therapy and to increase the survival rates for this category of patients.

Journal of Modern Oncology. 2021;23(2):340-344
pages 340-344 views

Modern approaches to the diagnosis of malignant trophoblastic tumors

Mamedli S.N., Chekalova M.A., Meshcheriakova L.A.

Abstract

Malignant trophoblastic tumors (TO) include invasive and metastatic cystic drift, choriocarcinoma, TO of the placental bed, and epithelioid TO. They are rare, mainly in women of reproductive age, and most importantly, they are always associated with pregnancy. To date, the Blokhin National Medical Research Center of Oncology has accumulated a large and unique experience of modern diagnostics and treatment of patients with various forms of malignant TO. An obligatory stage of the examination is ultrasound diagnostics of the pelvic organs. In addition, performing an ultrasound examination during the treatment period, along with monitoring the level of chorionic gonadotropin, makes it possible to assess the effectiveness of treatment, diagnose tumor resistance and ascertain the onset of remission.

Journal of Modern Oncology. 2021;23(2):345-348
pages 345-348 views

Modern approaches to the therapy of invasive mycoses in cancer patients

Prikhodchenko A.O., Nechuskina V.M., Vyatkin P.V.

Abstract

There is an increase in the prevalence of Candida fluco-R, there is a transition from strains of C. albicans to C. non-albicans. Diagnosis of invasive fungal infections is based on a clinical picture and risk factor assessment with subsequent retrospective confirmation of the diagnosis by a microbiological method. Echinocandines are the drugs of choice in the therapy of invasive/systemic mycoses in cancer patients.

Journal of Modern Oncology. 2021;23(2):349-353
pages 349-353 views

The importance of the prevention of treatment induced neutropenia in patients with malignant neoplasms of the head and neck

Abstract

Hematological toxicity is the most common complication of chemotherapy. The most dangerous manifestation of hematological toxicity is febrile neutropenia (FN). FN reduces survival, increases the risk of death, the frequency of infectious complications, hospitalizations, the cost of treatment. The risk of FN should be assessed before the beginning of the therapy, using the general algorithm from the protocol to prevent FN applying the granulocyte colony-stimulating factors (G-CSF). G-CSF for the prevention is required throughout all cycles of myelosuppressive therapy. For the prevention of FN, the most effective is the use of PEGylated G-CSF. Patients with head and neck squamous cell carcinoma, receiving the TPF or DCF regimen, combined with docetaxel and cisplatin, are included in the group of routine primary prophylaxis for neutropenia. In case of developing 3–4 grade FN in these patients, the use of PEGylated G-CSF (empegfilgrastim) is preferable.

Journal of Modern Oncology. 2021;23(2):356-360
pages 356-360 views

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