Vol 23, No 3 (2021)

CLINICAL ONCOLOGY

Malignant neoplasm of the bronchi and lung: Russian clinical guidelines

Laktionov K.K., Artamonova E.V., Borisova T.N., Breder V.V., Bychkov I.M., Vladimirova L.I., Volkov N.M., Ergnian S.M., Zhabina A.S., Kononets P.V., Kuz’minov A.E., Levchenko E.V., Malikhova O.A., Marinov D.T., Miller S.V., Moiseenko F.V., Mochal’nikova V.V., Novikov S.N., Pikin O.V., Reutova E.V., Rodionov E.O., Sakaeva D.D., Semenova A.I., Smolin A.V., Sotnikov V.M., Tuzikov S.A., Turkin I.N., Tiurin I.E., Chkhikvadze V.D., Kolbanov K.I., Chernichenko A.V., Fedenko A.A., Filonenko E.V., Nevol’skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G., Butenko A.V., Gil’mutdinova I.R., Gridneva I.V., Eremushkin M.A., Zernova M.A., Kasparov B.S., Kovlen D.V., Kondrat’eva K.O., Konchugova T.V., Korotkova S.B., Krutov A.A., Obukhova O.A., Ponomarenko G.N., Semiglazova T.I., Stepanova A.M., Tkachenko G.A., Khulamkhanova M.M.

Abstract

Lung cancer has the highest morbidity rate among all malignant tumors in men and the highest mortality rate in men and women in Russia. In total, 49 145 new cases of lung cancer were registered (diagnosed) in Russia in 2019. The majority of cases are related to exogenic carcinogens and mainly tobacco smoke. For several decades surgical resection with preoperative cytotoxic therapy was an optimal approach for maximal cure rate. This year recommendations were updated with new strategies including adjuvant anti-PD-L1 atezolizumab following completion of chemotherapy in PD-L1 positive patients and osimertinib for EGFR mutated cases. For this moment available data suggest the increase in disease free survival. Strategic approach to treatment for inoperable patients varies according to the status of driver mutations. New approach includes pretreatment option of testing for a wide spectrum of alterations with NGS based panels. Significant changes were incorporated into treatment of ALK mutated NSCLC with two new options of brigatinib for TKI naive patients and lorlatinib for those who progress on second generation drugs. Treatment strategy for patients without activating mutations is based on PD-L1 status. Tsis year recommendations included atezolizumab as a new monotherapy option for patients with high depression of PD-L1. Also treatment options for pembrolizumab, nivolumab and atezolizimab were widened with prolonged treatment schedules.

Journal of Modern Oncology. 2021;23(3):369-402
pages 369-402 views

ELEVATE-RR – first head-to-head trial of acalabrutinib versus ibrutinib in previously treated high risk chronic lymphocytic leukemia

Bialik T.E., Vorob'ev V.I., Ionin V.A., Ysebaert L., Kaplanov K.D., Mendeleeva L.P., Nikitin E.A., Ptushkin V.V., Samoilova O.S., Stadnik E.A.

Abstract

Over the past decades, there has been a significant expansion of the treatment options for patients with chronic lymphocytic leukemia (CLL) due to Bruton’s tyrosine kinase (BTK) inhibitors, which changed approaches in CLL therapy. Ibrutinib was the first BTK inhibitor approved for CLL treatment, but adverse events such as atrial fibrillation and hypertension may limit the use of ibrutinib. In the first head-to-head trial of acalabrutinib and ibrutinib ELEVATE-RR, acalabrutinib was statistically superior to ibrutinib in all-grade atrial fibrillation/flutter (9.4% vs 16.0%; р=0.023). In all-grade arterial hypertension (9.4% vs 23.2%) and grade ≥3 (4.1% vs 9.1%) acalabrutinib was statistically superior to ibrutinib. Acalabrutinib demonstrated fewer discontinuations due to adverse events (14.7%) vs ibrutinib (21.3%). Based on ELEVATE-RR results acalabrutinib should be considered as a drug of choice among BTK inhibitors for CLL patients, including patients with cardiovascular diseases and risks of cardiovascular diseases.

Journal of Modern Oncology. 2021;23(3):404-406
pages 404-406 views

Comparison of afatinib and osimertinib effect on overall survival in first-line drug treatment of EGFR-positive metastatic non-small cell lung cancer: network meta-analysis

Goryaynov S.V.

Abstract

Background. Tyrosine kinase inhibitors (TKIs) are the standard of treatment of EGFR-positive metastatic non-small cell lung cancer (mNSCLC). Different TKI generations have different properties. Currently there are no results of head-to-head clinical trials of II generation TKI afatinib against III generation TKI osimertinib. In such case network meta-analysis (NMA) can be used for evidence synthesis.

Aim. To compare afatinib and osimertinib effect on overall survival (OS) in first-line drug treatment of EGFR-positive mNSCLC.

Materials and methods. Search of trials to build evidence network was done in Medline, CT.gov, and EU-CTR. Endpoint was OS measured as hazard ratio (HR) of all-cause death. Analysis was split into base case analysis and two sensitivity analyses depending on criteria of transitivity. Random effect model was used for NMA. Results were analyzed in overall population and subgroups according to the type of EGFR-mutation, ECOG score, and presence of CNS metastases. Statistical analysis was done in R with netmeta package.

Results. Fourteen trials were included in the study. There was no statistically significant difference regarding OS between afatinib and osimertinib in overall population neither in base case nor in first sensitivity analysis: HR 1.06 [0.79; 1.41], p=0.697 and 1.08 [0.83; 1.41], p=0.561, respectively. Results of comparison of II generation TKIs against osimertinib in second sensitivity analysis were consistent: HR 1.03 [0.81; 1.31], p=0.834. Results in all subgroups were consistent with each other and overall population. There was no statistically significant heterogeneity/inconsistency in the network in any of the analyses.

Conclusion. Afatinib and osimertinib have similar efficacy regarding OS in first-line drug treatment of EGFR-positive mNSCLC.

Journal of Modern Oncology. 2021;23(3):408-417
pages 408-417 views

Network meta-analysis for clinicians

Bogdanov A.A., Bogdanov A.A.

Abstract

Decision making in clinical practice requires consideration of the relative efficacy and safety of medical interventions. A systematic review and meta-analysis, the results of which have the highest level of confidence in evidence-based medicine, only compare the effectiveness of two interventions, provided that there is a direct comparison between them in a set of randomized controlled trials. The development of statistical methods has led to the development of the network meta-analysis method, the application of which allows comparison for more than two interventions and even if the interventions were not directly compared in randomized controlled trials, but have a common comparison intervention. As a result, network meta-analysis is increasingly being used as an evidence base for the effectiveness of medical interventions. However, there are important assumptions and conditions underlying the performance of network meta-analysis. In this work, we tried to outline the main aspects of network meta-analysis that are important for clinicians in terms of its implementation and interpretation of its results.

Journal of Modern Oncology. 2021;23(3):418-424
pages 418-424 views

Antiangiogenic therapy in pretreated patients with lung adenocarcinoma without activating mutations: new features

Reutova E.V., Laktionov K.K.

Abstract

The possibilities of treatment of patients with metastatic non-small cell lung cancer have significantly expanded in the recent years. Several combined regimens of chemoimmunotherapy are currently being proposed as the first line, some patients with PD-L1 overexpression may be prescribed pembrolizumab or atezolizumab in monotherapy. Standard platinum-containing chemotherapy (PCT) has lost its position and is relevant only for contraindications to immuno-oncological (IO) drugs. The change in the standart of the first line inevitably led to the search for new optimal modes of the second line. The strategy of "angio-immunogenic switching" is promising – after progression on the regimens with IO, anti-angiogenic drugs are used. Nintedanib – a multikinase angiogenesis inhibitor in combination with docetaxel is a standard second-line therapy option in patients with lung adenocarcinoma after progression on PCT. The effectiveness of this regimen is being studied in a prospective non-interventional VARGADO study. The patients were divided into 3 cohorts, depending on which regimen was used earlier – one line of PCT or PCT, followed by IO or chemoimmunotherapy. The results showed that the combination of docetaxel + nintedanib was effective both as a third line (after PCT and IO), and in the second – after chemoimmunotherapy. The research is ongoing.

Journal of Modern Oncology. 2021;23(3):425-427
pages 425-427 views

Dual immunological blockade in the treatment of metastatic non-small cell lung cancer: reality and perspectives

Yudin D.I., Laktionov K.K., Laktionova L.V., Breder V.V.

Abstract

Nowadays immunotherapy is a crucial option in the treatment of non-small cell lung cancer. There are a lot of actual options of the first-line therapy for the patients with metastatic lung cancer, including dual immunological blockade of PD-1/PD-L1 and CTLA-4 pathways. This review is an attempt to clarify the place of dual immunological blockade now and in the future. The scientific rationale for dual immunotherapy is a possible synergy and overcome resistance to single-drug therapy. The review collected information from open sources, both current studies with dual immunological blockade, and already obtained results of the trials for nivolumab and ipilimumab, tremelimumab and durvalumab, and other combinations for the treatment of patients with metastatic non-small cell lung cancer. This approach is promising for the possible overcoming of resistance to monoimmunotherapy with anti-PD1/PD-L1 antibodies, especially in the population with low and negative PD-L1 status.

Journal of Modern Oncology. 2021;23(3):428-435
pages 428-435 views

Regorafenib in metastatic colorectal cancer: more data for clinical decisions

Petkau V.V., Karimova A.A., Akishina Z.V.

Abstract

Regorafenib is a multiple kinase inhibitor. It influences/blocks angiogenesis (VEGFR1-3, TIE2), proliferation (KIT, RET, RAF-1, BRAF), metastatic activity (VEGFR2-3, PDGFR), tumor immunogenicity (CSF1R), tumor microenvironment (PDGFR-α, PDGFR-β, FGFR1-2). Regorafenib has several indications including metastatic colorectal cancer. Efficacy and safety of regorafenib data from clinical trials (CORRECT, CONCUR, CONSIGN) and observational trials from real world (REBECCA, CORRELATE, RECORA, PMS, REGOTAS) are summarized and presented in this issue. State of the matter of molecular-biologic predictors (KRAS, PIK3CA ANG-2, VEGF-A, LDH, CCL5/CCR5, CA 19-9) and radiological predictors (RadioCORRECT and other trials) is highlighted. Regimens with dose modification and its influence on effectiveness and tolerability of regorafenib are described according to the data from ReDOS, RESET, REARRANGE trials. The results from retrospective trials comparing regorafenib and another approved for refractory metastatic colorectal cancer drug trifluridine/tipiracil are presented.

Journal of Modern Oncology. 2021;23(3):436-441
pages 436-441 views

Extrapulmonary small cell carcinoma. Literature review

Orel N.F., Poddubnaya I.V.

Abstract

The review shows the features of rare tumors – extrapulmonary small cell carcinomas (EPSCC). The possible approaches for the treatment of this unfavorable group of tumors are discussed. EPSCC can occur in every organ. The clinical course and morphology of EPSCC are similar to small lung cell carcinoma (SCLC). EPSCC belongs to the group of low-grade neuroendocrine tumors with high proliferative activity. There are a small number of publications in the literature concerning EPSCC. Basically, these publications concerning the various clinical cases with comments. Most often, EPSCC occurs in the female genital tract, gastrointestinal tract, genitourinary SCC and known cases of SCC of the head and neck. The cases concerning SCC in other organs are also described. For the treatment of EPSCC are usually applied guidelines developed for SCLC, and several publications on the use of immunotherapy in the treatment of EPSCC have already appeared. The analysis of the available literature let us suggest EPSCC is a big problem that requires a more in-depth study and consensus guidelines adoption for the management of these patients.

Journal of Modern Oncology. 2021;23(3):442-446
pages 442-446 views

Modern possibilities of therapy for primary cutaneous T-cell lymphomas: the first results of the use of brentuximab vedotin in the Russian Federation

Gorenkova L.G., Belousova I.E., Kravchenko S.K., Kovrigina A.M., Sidorova Y.V., Ryzhikova N.V., Lepik E.E., Shneyder T.V.

Abstract

Background. Primary cutaneous T-cell lymphomas are rare heterogeneous group of lymphoproliferative diseases characterized by primarily involving skin and subcutaneous adipose tissue. Half of these cases are mycosis fungoides (MF), for about 25% are cutaneous CD30+ lymphoproliferative diseases (CD30+ LPD): primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP). During the initiating treatment of patients with MF and Sézary syndrome (SS), carried out on the territory of the Russian Federation, for about 30% of patients are resistant to various therapeutic effects, especially in the later stages. The problem of the treatment of CD30+ LPD is extracutaneous dissemination in case of pcALCL, steadily relapsing course of LyP without symptom-free intervals. These characteristics of the therapy of cutaneous lymphomas demand for the need to search for new treatment options. Brentuximab vedotin, according to the results of the international randomized ALCANZA trial, has shown high efficiency in the treatment of cutaneous T-cell lymphoproliferative diseases.

Aim. To evaluate the efficacy of brentuximab vedotin application in patients with cutaneous T-cell lymphomas in adverse risk group received at least one line of systemic therapy.

Materials and methods. The study included 21 patients: 16 men and 5 women. The diagnosis of MF was verified in 8 patients, SS – in 5 patients, cutaneous CD30+ LPD – in 6 patients (5 patients – pcALCL, 1 patient – LyP) and a primary cutaneous peripheral T-cell lymphoma, unspecified in 2 patients. The diagnosis of cutaneous T-cell lymphoma was verified on the basis of the anamnesis of the disease, on the character of cutaneous lesions, on histological, immunohistochemical and in some cases on molecular genetic testing of the biopted sample of the skin (the assessment of T-cell receptor gene rearrangement).

Results. The late stages of the disease were diagnosed in 12 of 13 patients with MF/SS. Extracutaneous lesions were diagnosed in 57% of cases. The median of prior lines therapy was 3 (1–8 variants of treatment). The overall response to the treatment was achieved in 91% of cases (in 19 of 21 patients): the complete remission was obtained in 53% of cases, very good partial remission – in 31% of cases and partial remission – in 16% of cases. The progression of the disease was determined in 2 patients (after the first and fourth cycles). Some patients with partial remission as a result of therapy using brentuximab vedotin had the additional therapy (radiation therapy, interferon α, the cycles of systemic therapy) and these acts gave an option of achieving deeper antitumor response. The early relapse was diagnosed in 2 of 19 patients who had responded to the treatment. The treatment tolerability was acceptable, and the toxicity did not exceed the already known one described in earlier studies. Thus, the stable overall antitumor response had been persisting in 89% of patients (the median of the observation was 10 months).

Conclusion. The use of targeted therapy with brentuximab vedotin gave an option of achieving high treatment results in group of patients with advanced stages of the disease and inefficiency of several lines of therapy.

Journal of Modern Oncology. 2021;23(3):447-452
pages 447-452 views

Physical activity interventions for disease‐related physical and mental health during and following treatment in people with non‐advanced colorectal 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: McGettigan M, Cardwell CR, Cantwell MM, Tully MA. Physical activity interventions for disease‐related physical and mental health during and following treatment in people with non‐advanced colorectal cancer. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No.: CD012864. DOI: 10.1002/14651858.CD012864.pub2

Journal of Modern Oncology. 2021;23(3):453-454
pages 453-454 views

Physical therapy interventions, other than general physical exercise interventions, in children and adolescents before, during and following treatment for 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: Ospina PA, McComb A, Pritchard-Wiart LE, Eisenstat DD, McNeely ML. Physical therapy interventions, other than general physical exercise interventions, in children and adolescents before, during and following treatment for cancer. Cochrane Database of Systematic Reviews. 3 August 2021. DOI: 10.1002/14651858.CD012924.pub2

Journal of Modern Oncology. 2021;23(3):454-455
pages 454-455 views

Telephone interventions for symptom management in adults 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: Ream E, Hughes AE, Cox A, Skarparis K, Richardson A, Pedersen VH, Wiseman T, Forbes A, Bryant A. Telephone interventions for symptom management in adults with cancer. Cochrane Database of Systematic Reviews 2020, Issue 6. Art. No.: CD007568. DOI: 10.1002/14651858.CD007568.pub2

Journal of Modern Oncology. 2021;23(3):455-456
pages 455-456 views

The relationship of GITR, Lag-3 and PD-1 expression with the main indicators of systemic and local immunity in patients with breast cancer

Tabakov D.V., Zabotina T.N., Chanturia N.V., Zakharova E.N., Vorotnikov I.K., Selchuk V.Y., Sokolovskiy V.V., Petrovsky A.V.

Abstract

Background. To enhance the antitumor immune response, new promising methods of immunotherapy are being developed. They consist in the blockade and activation of immune check-point molecules, in particular, the blockade of the Lag‐3 molecule (lymphocyte-activation gene 3) and the activation of the GITR receptor (Glucocorticoid induced TNF receptor). In the studies of combined use with PD-1 blockers, encouraging results were obtained, which makes the assessment of the expression of Lag-3 and GITR on immunocompetent cells of peripheral blood (PB) and tumor tissue necessary for the personalization of such treatment and understanding of the mechanisms of the antitumor immune response.

Materials and methods. The study included peripheral blood samples and surgical material from 39 breast cancer patients being treated at the Blokhin National Medical Research Center of Oncology. The subpopulation composition and expression of PD-1, Lag-3, and GITR molecules were evaluated by flow cytometry.

Results. The analysis of the main populations of PB lymphocytes showed that in patients with breast cancer, the content of NKT-lymphocytes was increased, and the proportions of lymphocytes expressing CD11b and CD25 markers were increased compared to the donor group. It was revealed that the tumor tissue is dominated by T-cells, an increase in the proportion of which occurs due to a reduced content of NK-lymphocytes and B-lymphocytes. The structure of Tumor-infiltrating lymphocytes (TILs) is dominated by subpopulations with immunosuppressive activity, which is indicated by a decrease in the content of CD11b+, CD25+ and perforin-positive cells, increased expression of Lag-3 and PD-1. For PB and tumor tissue, the average degree of dependence of Lag-3 expression on the content of PD-1+ lymphocytes was shown. There is an increase in the content of immunosuppressive subpopulations with high PD-1 values in PB and TILs. The direct dependence of the number of perforin-containing lymphocytes and CD11b expression on the GITR content in the PB was established, but it is not typical for breast cancer tissue.

Conclusion. Since the blockade of the Lag-3 molecule by monoclonal antibodies can enhance the effect of anti-PD-1 therapy in cancer patients, it is necessary to evaluate the expression and co-expression of these two markers. A high content of GITR-positive lymphocytes in the tumor tissue, on the one hand, and a decrease in the proportion of effector subpopulations of lymphocytes, on the other, indicates the influence of the tumor microenvironment on the functioning of GITR-mediated activation of the immune response. Further investigation of GITR expression and functional activity is required to understand the nature of this contradiction.

Journal of Modern Oncology. 2021;23(3):457-465
pages 457-465 views

Can any breast skin thickening be staged as T4?

Amosova V.A., Petrovskii A.V., Karpova M.S., Ponedel’nikova N.V., Frolova M.A.

Abstract

Data analysis showed that many diagnostic issues in breast cancer patients with skin involvement are not systematized. In some cases when the tumor is small and skin involvement symptoms are minimal ("local" skin edema), should this category of patients be considered as patients with non-inflammatory skin involvement breast cancer? Current research confirms the presence of skin involvement has much less prognostic value than, for example, tumor size or lymph node metastases, and the surgical term "unresectable" may not always be adequate. In addition, clinical data often do not correspond to pathological data, which also complicates the staging and leads to "overtreatment" of such patients. Thus, further research is needed to identify categories of breast cancer (patients with skin involvement similar in prognosis, as well as to individualize approaches to local and systemic treatment.

Journal of Modern Oncology. 2021;23(3):466-469
pages 466-469 views

Place of CDK 4/6 and PARP inhibitors in the modern treatment approach of HER2-negative breast cancer

Abstract

Three educational and discussion events with 35 key specialists from federal and regional cancer centers representing 7 federal districts were organized by Pfizer with the support of TS Oncology. The events were organized on the basis of the "OncoForum" platform (virtual platform developed and operated by TS Oncology). Experts shared their opinion on CDK4/6 inhibitors and PARP inhibitors place in the optimal therapy strategy for patients with HR+/HER2- metastatic breast cancer (mBC) and BRCA-associated HER2- mBC in Russia. This review presents results of the discussions on practical aspects of defining the optimal profiles of patients with HR+/HER2- mBC and BRCA-associated HER2- mBC for using CDK4/6 inhibitors and PARP inhibitors, evaluating the efficacy data and toxicity profiles for each of the CDK4/6 inhibitors and PARP inhibitors, as well as market access specifities for CDK4/6 inhibitors to patients with HR+/HER2- mBC and PARP inhibitors to patients with gBRCA-associated HER2- mBC in different regions of the Russian Federation.

Journal of Modern Oncology. 2021;23(3):470-476
pages 470-476 views

Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer

Ognerubov N.A.

Abstract

The incidence of prostate cancer in the structure of malignant neoplasms occupies the fourth place, it is 7.3%. 1 414 259 new cases and 375 304 deaths were estimated worldwide in 2020. In recent decades, there was a significant increase in the number of cases of metastatic castration-resistant prostate cancer (mCRPC). There is no consensus on the optimal treatment choice, nowadays. The various therapeutic options are offered for these aims. But, the regimes and the consistence of their application are problematical and far from being resolved. The aim of this review is to analyze the studies on the use of cabazitaxel in the treatment of mCRPC. The history of the taxanes application in advanced and metastatic prostate cancer dates back to 2004, when the United States Food and Drug Administration registered docetaxel as first-line therapy for patients with metastatic prostate cancer. Cabazitaxel – the new second generation taxane appeared in 2010, and showed the activity in the development of castration resistance. The drug demonstrated high antitumor activity and significant efficacy at the time of progression against the background of treatment with docetaxel and androgen receptor inhibitors. The results of the number of the randomized clinical trials associated with the various aspects of treatment tactics in mCRPC are available for the analysis, nowadays. However, these data and especially the clinical benefit are ambiguous, and sometimes contradictory. The review presents the results of the scientific researches, international clinical studies concerning the various aspects of mCRPC, in particular the choice of modern optimal treatment tactics.

Journal of Modern Oncology. 2021;23(3):477-488
pages 477-488 views

Circulating and disseminated tumor cells as a possible prognostic factor for oncological diseases

Kaprin A.D., Zatsarenko S.V., Ivanov S.A., Grivtsova L.Y.

Abstract

Background. Distant metastasis remains the main cause of death for patients, despite some successes in the diagnosis and treatment of solid tumors. This demonstrates the significance to study the methods for the timely detection of tumor micrometastases and to find the role of tumor cells preserved in peripheral blood or disseminated tumor cells in bone marrow after the end of the treatment.

Aim. To generalize the data concerning the significance and methodology of the determining circulating tumor cells in peripheral blood and disseminated tumor cells in bone marrow in case of different types of cancer.

Materials and methods. Foreign and domestic articles concerning this topic, published in eLibrary, PubMed, Medline, Scopus databases have been analyzed.

Results. The literary review deals with the modern methods of determination, we have analyzed the importance of identification of circulating and disseminated tumor cells as the clinical predictors for specific nosological types of cancer.

Conclusion. The enumeration of circulating and disseminated tumor cells could be a new generation of screening and evaluation of the efficacy of cancer therapy. However, it is necessary and up to date to develop the methodology of their quantitative and qualitative identification and to find the methods for evaluating functional activity.

Journal of Modern Oncology. 2021;23(3):490-495
pages 490-495 views

The phenomenon of pseudoprogression in cancer immunotherapy: is everything so unambiguous?

Sarzhevskiy V.O., Melnichenko V.I., Panshina I.V., Mochkin N.E., Bogatyrov V.S., Borshevetskaya M.M., Smirnova E.G., Bannikova A.E., Samoylova A.A., Mamedova A.A., Rukavitsin A.A., Vasilev S.S., Bronov O.I.

Abstract

When evaluating the effect of therapy for malignant neoplasms with inhibitors of CTLA-4, PD-1 and PD-L1, the phenomenon of pseudoprogression may occur. Pseudoprogression is an increase in the volume of tumor tissue due to immunocompetent cells (lymphocytes, macrophages) mobilized into the tumor focus under the action of immunotherapy. As the antitumor effect of lymphocytes and macrophages is realized, the tumor decreases or disappears over time. Pseudoprogression occurs with varying frequency in various types of cancer. It may also matter which immune checkpoint inhibitors is used to treat a solid tumor or lymphoproliferative disease. Currently, several immune-related response-evaluation criteria have been developed, which can help diagnose the phenomenon of pseudoprogression. But, unfortunately, none of these criteria clearly distinguish pseudoprogression from true tumor progression. In the case of an erroneous judgment about the effect of treatment, immunotherapy ends, and the patient may not get a chance for long-term remission. Using two clinical examples (immunotherapy for metastatic kidney cancer and recurrent Hodgkin lymphoma), the authors discuss the pitfalls of evaluating the effectiveness of treatment with checkpoint inhibitors.

Journal of Modern Oncology. 2021;23(3):496-500
pages 496-500 views

Malignant neoplasms associated with HIV infection. Problems and solutions (problem outline)

Kaprin A.D., Voronin E.E., Rassokhin V.V., Rozenberg V.V., Nekrasova A.V., Falaleeva N.A., Ivanov S.A., Grivtsova L.Y.

Abstract

HIV infection refers to socially significant diseases. As a result of the wide coverage of effective antiretroviral therapy for people living with HIV, the rates of AIDS-related mortality have significantly decreased. At the same time, there was a noticeable increase in morbidity and mortality from other non-AIDS-related diseases, not the last place in this list is occupied by malignant neoplasms. A decrease in the frequency of AIDS-associated tumors and an increase in the proportion of AIDS-unassociated tumors are significant changes in the structure of malignant neoplasms. There is a complex relationship between HIV-induced immune suppression, chronic antigenic stimulation and concomitant oncogenic viral infections, which increases the risk of developing malignant tumors in these patients. People living with HIV have higher rates of cancer mortality associated with both the lack of adequate antitumor therapy, complications of treatment, and the existence of a direct relationship between immunosuppression and tumor progression. This article analyzes the problems that arise in the treatment of oncological HIV-infected patients, and offers specific practical steps to solve complex interdisciplinary problems.

Journal of Modern Oncology. 2021;23(3):502-507
pages 502-507 views

The modified biopsy technique conducting ultrasound bronchoscopy with endosonographic-guided position of the endoscopic instrument in the area of the pathological focus. The results of the first phase of the clinical trial

Pushkarev E.A., Vazhenin A.V., Kulaev K.I., Iusupov I.M., Zuikov K.S., Popova I.A.

Abstract

Background. The problem of diagnostics and treatment of malignant neoplasms of the lungs is urgent. Verification of a malignant process in the case of peripheral localization of a neoplasm in the lung using ultrasound bronchoscopy ranges from 30 to 85%. To improve the efficiency of ultrasound bronchoscopy, a modified biopsy technique for ultrasound bronchoscopy was developed and introduced into clinical practice at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine. The essence of the modified technique is that it becomes possible for ultrasound visual control over the passage and deployment of biopsy forceps in real time. The technique was patented, patent for invention RU №2719666 C1 was issued.

Aim. To clarify the information content of ultrasound bronchoscopy using a modified technique.

Materials and methods. On the basis of the endoscopic Department of Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine in 2019 and 2020, ultrasound bronchoscopy using this technique was performed on 40 patients with suspected peripheral malignant neoplasm of the lungs. The diagnosis of malignant neoplasm was verified in 67.5% of cases. Using the standard biopsy technique, the probability of verification of lung malignant neoplasms in 2019 and 2020 was 57.7%. Thus, the modified biopsy technique made it possible to increase the verification probability by 9.8%. The modified technique is relatively safe, complications during the procedure were detected in 2 patients (in 3.8% of cases) and were successfully treated conservatively. During and after the procedure, the patients were monitored and monitored. The ultrasound bronchoscopy according to the modified technique was satisfactorily tolerated by the patients.

Results. The period of examination of patients when using this technique does not increase. The technique replaces more invasive diagnostic procedures.

Conclusion. The use of the modified technique will improve the information content of ultrasound bronchoscopy, shorten the examination time for patients and accelerate the appointment of special treatment methods.

Journal of Modern Oncology. 2021;23(3):508-512
pages 508-512 views

V-shaped radial forearm free flap is a new way to reduce the morbidity of the donor area

Bolotin M.V., Mudunov A.М., Sobolevsky V.Y., Akhundov A.А., Gelfand I.М., Sopromadze S.V.

Abstract

Background. Radial forearm free flap is one of the most frequently used in the head and neck reconstruction. A significant disadvantage is the appearance of the donor site. We have developed and introduced into clinical practice a V-shaped fabrication skin of the flap, which allows “direct” closure of the donor site and reduces morbidity.

Aim. To assess the possibility of “direct” closure of the donor site and to reduce the morbidity of the donor site when performing the V-shaped fabrication of the skin area of the flap.

Materials and methods. During the period from 2014 to 2020, the radial free flap was used in 43 cases. In 15 (35%) cases, a V-shaped fabrication of the skin area was used during flap harvest, which made it possible to carry out a “direct” closure of the donor site. The length of the skin area stretched from the top of the wrist, not reaching 3–4 cm to the elbow bend and varied from 7–15 cm, on average – 12 cm. The width of the flap was determined by the elasticity of the forearm skin, was maximum in the middle third and varied from 2 up to 4 cm, averaging 3.3 cm. If necessary, the upper and lower edges of the skin area can be sutured together, as well as the entire medial edge of the flap. This technique increases the flap width by almost 2 times. This arrangement was applied in 8 cases.

Results. When comparing the results of using the two techniques, the following data were obtained: "V-shaped" fabrication of the skin was used mainly in women (11/15 – 73%) for reconstruction limited defects in the retromolar region (5/15), soft (4/15) or hard palate (6/15). Most of the patients had localized T1-T2 (10/15) stage. None of the patients had any problems with the healing of the donor area. An excellent aesthetic result was obtained in all patients. In the group of standard harvest, the predominance of males was noted (17/28). Defects had a varied localization, most patients was with relapses after chemo-radiation treatment (10/28) or primary locally advanced T3-T4 stage process (6/28) – 16, with a localized T1-T2 stage (11/28) – 11, in one case, delayed reconstruction was performed. In all cases, the plastic of the donor site was performed with a split skin autograft. Partial necrosis of the donor site flap was observed in 9 patients (32%), in 4 cases with exposure of the flexor muscle tendon.

Conclusion. As a result of the comparative analysis of the two methods, we concluded that the use of V-shaped fabrication of the skin area of the radial forearm flap allows to obtain better aesthetic results of the donor site, however, the use of this technique leads to a significant reduction in the length of the vascular pedicle and a decrease in the width of the flap.

Journal of Modern Oncology. 2021;23(3):513-517
pages 513-517 views

Influence of correction of nutritive deficiency on the effectiveness of neoadjuvant chemotherapy in patients with locally advanced gastric cancer

Brish N.A., Semiglazova T.Y., Karachun A.M., Shevkunov L.N., Ulyanchenko Y.A., Artemyeva A.S., Golovanova T.S., Tkachenko E.V., Alexeeva Y.V., Sharashenidze S.M., Strakh L.V., Protsenko S.A., Teletaeva G.M., Filatova L.V., Kasparov B.S., Semiglazov V.V., Belyaev A.M.

Abstract

Aim. To increase the effectiveness of neoadjuvant chemotherapy in patients with locally advanced gastric cancer by correcting nutritional deficiency.

Materials and methods. Of 200 patients with locally advanced gastric cancer (mean age 57.2 years (46.1–68.3), 100 patients received neoadjuvant chemotherapy with nutritional support from 2018 to 2020. One hundred patients received neoadjuvant chemotherapy without nutritional support from 2013 to 2018 (historical control). The incidence of nutritional deficiency before treatment in the “neoadjuvant chemotherapy + nutritional support” group was 54%, and in the “neoadjuvant chemotherapy only” group it was 47%. Nutritional status was assessed using anthropometry, questionnaires (NRS-2002, MUST, GLIM), dynamometry, blood tests, bioimpedance. Complications according to NCI CTCAE v5.0; оbjective response rate according to RECIST 1.1; pathomorphological regression according to the JGCA classification (2017); 2-year event-free survival were assessed.

Results. The frequency of nutritional deficiency before the start of treatment in the “neoadjuvant chemotherapy + nutritional support” group was 54%, in the “neoadjuvant chemotherapy only” group – 47%. After the completion of neoadjuvant chemotherapy in the group “neoadjuvant chemotherapy + nutritional support” the frequency of nutritional deficiency was 1%, in the group “neoadjuvant chemotherapy only” without nutritional support – 62%. In patients with nutritional deficiency in the “neoadjuvant chemotherapy + nutritional support” group, partial regression was registered in 51.9% of cases, in the “neoadjuvant chemotherapy only ”group it was 27.6% (p<0.05). There were no differences in the frequency of pathological response. 2-year event-free survival in patients without nutritional deficiency in the group “neoadjuvant chemotherapy + nutritional support” was 100%, in the “neoadjuvant chemotherapy only” group it was 68.5% (p<0.001); in patients with nutritional deficiency – 72,5 and 60.6% respectively (p<0.05).

Conclusion. Nutritional deficiency is an important predictive and prognostic marker of the efficacy of neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Comprehensive diagnosis of nutritional status and nutritional support can improve the results of neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

Journal of Modern Oncology. 2021;23(3):519-524
pages 519-524 views

Clinical and morphological case of lung cancer with generalized metastases to the internal organs

Vorobeva O.V.

Abstract

Lung cancer has occupied a leading position in the structure of cancer morbidity and mortality throughout the world for many years. Lifetime diagnosis is often difficult due to the absence of any defining signs of cancer, and it is quite difficult to track the first signs of lung cancer. This is justified by the fact that the lungs are completely devoid of nerve endings and the presence of 26% of healthy lung tissue is sufficient to provide the body with the required amount of oxygen. Prolonged absence of clinical manifestations leads to late seeking medical help, which is often fatal. Description of the case. A 65-year-old patient who died at home was referred for a postmortem examination. The sectional study revealed signs of peripheral cancer of the right lung with multiple metastases in all fields of the lungs, in the liver, spleen, pancreas, with no metastases in the lymph nodes. Histological examination revealed extensive areas of tumor tissue, consisting of solid structures with glandular differentiation of tumor tissue of various sizes and shapes, with round and oval atypical nuclei. There was a pronounced polymorphism of cells, with a large number of pathological mitoses. Thrombi were detected in the lumen of the segmental and small branches of the pulmonary artery. Thus, the presented case is of particular interest for practicing physicians due to the fact that with adenocarcinoma of the lung, there were no characteristic metastases to the lymph nodes. Hematogenous metastasis occurred with the development of generalized metastases to the internal organs.

Journal of Modern Oncology. 2021;23(3):525-528
pages 525-528 views


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