Vol 25, No 1 (2023)

The emergence of new drug therapy regimens and the completion of several large randomized trials led to significant changes in the clinical guidelines of the Ministry of Health of Russia and the practical guidelines of the Russian Society of Clinical Oncology (RUSSCO) for the treatment of urologic oncology diseases. However, different interpretations of some studies by expert panels and requirements for these documents led to a divergence of some statements in these publications. The article presents executive summaries of the updated clinical and practical prostate cancer treatment guidelines.

Background. Melanoma of the skin is characterized by a rapid progression and early metastasis. It has been shown the disseminated tumor cells, which are often found in the bone marrow, has an important prognostic value. The study of disseminated tumor cells in melanoma might be one of the possible additional sources of information about the nature of the disease and potential application points for drug therapy.

Aim. To study the frequency of detection of disseminated tumor cells in the bone marrow in melanoma, depending on the clinical and morphological characteristics of the tumor.

Materials and methods. The study included 67 patients with a verified diagnosis of melanoma who were examined and treated at the Blokhin National Medical Research Center of Oncology from 2014 to 2019 years. Male patients accounted for 50.7% (n=34), female patients 49.3% (n=33). The average age of patients: 50.1±1.6 years. Immunological and morphological examination of the bone marrow were perfomed. Morphological examination was performed by two independent morphologists. Disseminated tumor cells were evaluated by flow cytometry among all nucleated cells (Syto41+) based on the expression of the HMB-45 antigen and the absence of expression of the CD45 panleukocyte antigen (FACS Canto II, USA, Kaluza Analysis v2.1). Statistical data processing was performed using the IBM-SPSS Statistics v.21

Results. Morphologically bone marrow damage was not detected in any case. Disseminated tumor cells (CD45-HMB-45+) in the bone marrow of melanoma patients were detected in 62.7% (n=42) of cases by flow cytometry. The frequency of bone marrow damage in the early stages is not lower than in advanced ones (p=0.029). This is clearly seen in the enlarged analysis. The percentage of DTC detection. At stages I and II was 60.0% (6/10) and 84.6% (11/13), respectively, at stages III and IV – 44.4% (8/18) and 65.4% (17/26). In addition, the frequency of detection of disseminated tumor cells in the bone marrow was higher in young patients (p=0.02). There was no correlation between the frequency of bone marrow damage depending on BRAF status.

Conclusion. The connection of disseminated tumor cells with the clinical and morphological characteristics of the melanoma has been established. Melanoma is characterized by frequent bone marrow damage, even in the early stages, in young patients.

A review of the data presented at the SABCS 2022 conference on the treatment of advanced breast cancer (metastatic breast cancer – mBC) was conducted; 12 of the most exciting, creative, and significant randomized and population studies were identified, the results of which were reported at oral or poster sessions. For the first time, new and unique data on the treatment of HR+HER2-negative mBC from the following studies were presented: RIGHT Choice phase II randomized clinical study (combination endocrine therapy with ribociclib versus chemotherapy in aggressive disease, including visceral crisis), PACE study (combination endocrine therapy with palbociclib after disease progression on CDK4/6 inhibitors), and several studies on choosing the optimal treatment strategy for hormone-resistant breast cancer (CAPItello-291, EMERALD, SERENA-2, TROPiCS-02). A clear-cut favorite, trastuzumab deruxtecan, became available in treating pre-treated HER2+ mBC; at the SABCS 2022 conference, new data from a randomized phase III clinical trials (DESTINY-Breast 02 and 03) and two large real-world population analyses from Italy and Japan were presented. Among the studies on advanced triple-negative mBC, noteworthy are the results of two extraordinary phase II clinical studies, DORA and ALICE, which studied the effectiveness and safety of immunotherapy with unusual combinations (with olaparib in the DORA study and with immunomodulatory chemotherapy in the ALICE study).

Background. One of the main stages of the treatment of breast cancer (BC) is endocrine therapy with tamoxifen or aromatase inhibitors. Five years of adjuvant tamoxifen therapy reduces the risk of disease recurrence by 39%. Tamoxifen was approved by the U.S. Food and Drug Administration in 1977 as a treatment for ER-positive BC. However, sometime after the start of tamoxifen's wide use, reports have been published on its long-term adverse effects. Most common were hot flashes, gynecological symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep changes, weight gain, and decreased libido. However, more serious adverse events such as venous thromboembolic disease and endometrial hyperplasia or cancer are the most clinically significant. The article presents the results of a retrospective population-based study on assessing hyperplastic processes of the endometrium (HPE) in patients with breast cancer during TAM therapy, conducted in 2017, approved by the Ethics Committee of the Scientific Research of the Russian Medical Academy of Continuing Professional Education.

Aim. To identify clinical factors that may increase the risk of HPE during tamoxifen therapy in patients with a history of breast cancer living in the Moscow region.

Materials and methods. We retrospectively reviewed 230 case histories of patients with breast cancer. Of these, 120 patients who received TAM therapy had the following HPE risk factors: average age, menopausal status, body mass index, and duration of TAM therapy.

Results. It was found that patients with HPE taking TAM were older (p=0.017), more likely to be postmenopausal (p=0.035), overweight (p=0.023), and received TAM for a longer period (p=0.028) than patients without HPE.

Conclusion. The data obtained indicate the need for continuous monitoring by gynecologists of patients with breast cancer taking tamoxifen, paying particular attention to women from high-risk groups, namely older postmenopausal women with high body mass index receiving TAM for more than 1.5–2 years.

Background. During last 50 years there was a significant progress in understanding the nature of pediatric acute lymphoblastic leukemia (ALL). There were developed effective chemoradiotherapy regimens, new methods of diagnosis and emerged evaluation of treatment results. Determination of minimal residual disease (MRD) has become the most important factor in the patient’s stratification for risk-adapted treatment in the ALL IC-BFM 2009.

Aim. To evaluate the survival rates of children with ALL according to the ALL IC-BFM 2009 protocol.

Materials and methods. There were 136 people in the study of evaluating the effectiveness of therapy according to the ALL IC-BFM 2009 protocol: 69 boys and 67 girls (ratio 1.03:1). The median age is 4 years and 10 months. The observation period is from 26.01.2010 to 06.11.2022.

Results. High survival rates of children with newly diagnosed ALL are achieved: overall survival (OS) is 91.2%, event-free (EFS) – 82.4%, relapse-free (RFS) – 88.6%. The best results are among patients of the standard risk group: OS, EFS and RFS reach 96.6%. In the intermediate group OS – 96.2%, EFS – 84.8% and RFS – 88.3%. Worse results of survival are in the high risk group: OS – 76.9%, EFS – 65.4% and RFS – 80.7%. Outcome analysis depending on the linear reveals a statistically insignificant difference in survival rates (for B-ALL OS – 92.4%, EFS – 83.1% and RFS – 89.5%, for T-ALL OS – 83.3%, EFS – 77.8% and RFS – 83.3%). It determines the tendency of improving the prognosis of pediatric T-ALL by optimizing the stratification of patients based on the indicators of MRD and the best direction of protocol.

Conclusion. Results of survival rates of patients with ALL confirm high effectiveness of treatment according to the ALL IC-BFM 2009 protocol. MRD level on day 15 makes it possible to stratify patients and choose the optimal risk-adapted therapy.

Background. The combination of several diagnostic methods is used to predict treatment outcomes, assess overall survival, and increase the positive predictive value of detecting malignant lung and bronchial tumors.

Aim. To evaluate the diagnostic value of the CLIA-СА-62 chemiluminescence immunoassay reagent kit for the detection of early (Ia–IIb) and advanced (IIIa–c) stages of lung cancer (LC) in a double-blind clinical study and to assess the use of the CA-62 cancer antigen as a supportive decision-making tool in LC diagnosis in patients with suspicious changes on the tomogram or as a tool for pre-screening of LC prior to computed tomography (CT) to increase diagnostic sensitivity in the detection of early (I and II) stages of LC.

Materials and methods. A blinded clinical study was conducted on 304 clinically verified serum samples, including 141 samples from patients with non-small cell LC (NSCLC), 133 healthy volunteers, and 30 chronic obstructive pulmonary disease patients. Quantification of other well-known tumor markers used in the diagnosis of LC (CEA, CA-125, CA 15-3, CA 19-9, CYFRА 21-1, NSE, and SCC), as well as the CA-62 marker in all serum samples was performed using electrochemiluminescent immunoassay Elecsys CA-125, ELECSYS CA 19-9, ELECSYS CYFRА 21-1 and ELECSYS SCC (COBAS, Roche Diagnostics GmbH, Germany, EU), enzyme-linked immunoassay CA 15-3-ELISA-BEST, CEA-ELISA-BEST, NSE-ELISA-BEST (AO Vector-Best, Russia) and chemiluminescent immunoassay CLIA-СА-62 (JVS Diagnostics, Skolkovo, Moscow, Russia).

Results. CA-62 glycoprotein showed the highest level of expression at stage I NSCLC (12 745 U/mL) compared to other tumor markers studied and remained very high at the later stages of cancer: stage II (11 261 U/mL) and stage III (10 220 U/mL). A comparative analysis of the ROC curves of the most promising tumor markers CEA, CYFRA 21-1, SCC, and CA-62 for the entire NSCLC cohort versus all healthy volunteers and patients with chronic obstructive pulmonary disease showed a significant difference in the area under the curve between CA-62 (AUC 0.981) and other markers: CEA (AUC 0.84)> CYFRA 21-1 (AUC 0.753)>SCC (AUC 0.682). When detecting early stages (I and II) of NSCLC, a comparison of the sensitivity of the studied tumor markers showed the following pattern: CA-62 (92%)>CEA (37%)>CYFRA 21-1 (9%) and SCC (9%)>NSE (4.5%)>CA-125 (3%)>CA 15-3 (1.5%)>CA 19–9 (1%). In contrast to the CEA, CA 15-3, CA-125, NSE, CA 19-9, CYFRA 21-1, and SCC tumor markers, which are expressed proportionally to tumor growth, the epithelial carcinoma marker CA-62 showed the highest diagnostic indicators in the detection of LC early stages (I–II): sensitivity 92.5%, specificity 96.3%, positive predictive value 91.2%, NPV 97%, with 95% accuracy of LC detection with biopsy.

Conclusion. The study results showed that in order to increase the specificity of computed tomography in diagnosing LC in patients with suspicious lesion on the CT scan on the tomogram, the use of the carcinoma-specific marker CA-62 can improve the interpretation of the localized focus visualized and increase the accuracy of differential diagnosis at the early stages of LC to 96%, thus contributing to an increase of the overall survival among patients with lung cancer. Of the entire panel of markers, only glycoprotein CA-62 showed a strong correlation with histology (kappa 0.91) in identifying the malignant process with inconclusive results of low-dose CT (LDCT). In the future, introducing the CA-62 marker to the current system for assessing the LC risk as a pre-screening for LDCT can improve the detection of early LC by reducing false-positive results. Once introduced into existing screening programs, it can help significantly reduce the number of patients who need LDCT, decreasing the workload of LDCT and reducing radiation exposure.

Among all histological types, serous carcinomas account for up to 85%. Due to pronounced heterogeneity (at the molecular and genetic level) and chemoresistance, difficulties arise in finding active targets for tumor elimination.

Aim. To establish a link between the population composition of tumor-associated immune cells of the microenvironment and the stage of serous ovarian cancer.

Materials and methods. The analysis of the pathologic and anatomical material in 74 patients with serous ovarian cancer was carried out. Monoclonal antibodies were used to determine antigens in the samples: CD3, CD4, CD8, CD11b, CD14 and CD16.

Results. The obtained results of the immunohistochemical study showed that in the composition of the immune cells of the microenvironment, the largest number of cells, at all stages (I–IV) of the oncological process, are represented by macrophages (CD11b+, CD14+), CD3+ lymphocytes are in second place in terms of the number of cells, followed by CD8+ and CD4+ and the smallest number of CD16+ cells.

Conclusion. As a result of the immunohistochemical study, a multidirectional trend was found between the population composition of tumor-associated immune cells of the microenvironment and the stage of serous ovarian cancer. With an increase in the stage of the disease, the number of macrophages (CD11b+, CD14+) and lymphocytes (CD3+, CD16+) decreased regardless of the degree of differentiation of the tumor. With an increase in the tumor stage, the number of CD4+ and CD8+ populations decreased, but in this case, the degree of differentiation played a significant role, i.e. the higher the tumor stage and the lower the degree of differentiation, the fewer cells were detected.

Background. The results of several multicenter studies indicate a high risk of severe COVID-19 and fatal outcomes in immunocompromised patients, including those with cancer. Effective prevention is critical to saving cancer patients' lives during the pandemic. Additional passive immunization with a combination of monoclonal antibodies to the SARS-CoV-2 S protein in clinical studies showed a significant reduction in the risk of severe disease and death and a decrease in the frequency of hospitalizations. Real clinical practice shows the high efficiency of this approach in patients with oncological diseases receiving immunosuppressive therapy.

Aim. To perform a comparative analysis of prevention effectiveness and COVID-19 severity in patients with solid malignant tumors receiving antitumor drug therapy.

Materials and methods. The analysis included 100 vaccinated patients aged 22 to 84 with metastatic or inoperable solid tumors who received cytostatic therapy with or without a targeted agent. The median age was 56.5 years in Group 1 and 57.7 years in Group 2. In both groups, 32 (64%) patients had breast cancer, 10 (20%) had gastric, colon, and rectal cancers, 2 (4%) had lung cancer, 4 (8%), and 6 (12%) had reproductive cancers. In addition, Group 1 included 1 patient each with bladder and brain cancer. All were treated with antitumor drug therapy following clinical guidelines according to tumor localization.

Results. The median number of received treatment lines of patients in Group 1 was 2.2, and 2.38 in Group 2. In Group 1, 42% of patients got infected, and 64% in Group 2. The combination of tixagevimab 150 mg + cilgavimab 150 mg monoclonal antibodies reduced the incidence of COVID-19 infection in any clinical form by 1.5-fold and hospitalizations by 1.3-fold. In Group 1, the rate of mild COVID-19 was higher; in Group 2, a higher risk of severe course was observed. In Group 1, viral pneumonia was 1.6-fold less common than in Group 2. Overall mortality in Group 1 was 6.5-fold lower than in Group 2. In Group 1, no COVID-19-related deaths were registered; in Group 2, the mortality rate was 8% (n=4). Mortality related to underlying disease in Group 2 was 3.5 times higher, and the risk of dying from the malignant tumor progression was 50% higher. In addition, in Group 2, 15% of deaths were related to cardiovascular diseases.

Conclusion. Adding Evusheld to vaccinated patients significantly reduces the burden of COVID-19 infection in individuals with solid neoplasms who are receiving antitumor drug therapy. Patients receiving Evusheld at any stage of the underlying disease are less likely to have COVID-19, including severe infection, which requires hospitalization in an infectious hospital. The reduction in overall mortality in the Evusheld group suggests that COVID-19 affects overall survival in cancer patients. Evusheld reduced the risk of death in cancer patients from any causes: the progression of malignant tumors, COVID-19 infection, and other comorbidities.

Mutation in the BRAF V600E gene in metastatic colorectal cancer (CRC) occurs in 5–10% of cases and is a significant problem due to the aggressive course and extremely unfavorable prognosis. In recent years, new treatment options for BRAF mutated CRC have been emerging, for example, combinations of BRAF inhibitors, anti-EGFR antibodies with optional addition of MEK inhibitors. The possibility of local treatment methods is also being discussed. Objective: to evaluate the effectiveness of triple targeted therapy in BRAF-mutated metastatic colorectal cancer. On the example of 2 clinical cases of long-term treatment of patients with this molecular subtype, possible treatment options are discussed.

Background. The only effective treatment for renal cell carcinoma with tumor inferior vena cava (IVC) thrombosis is surgery. Nephrectomy with thrombectomy (NETE) is usually associated with clinically significant blood loss. The role of blood-sparing methods using autoerythrocyte reinfusion device (ARD) or replacement of blood loss with donor erythrocytes (DE) on the outcomes of NETE has not been well studied.

Aim. To study the rate of hemostasis disorders with intraoperative ARD use, as well as the effect of ARD and DE transfusions on specific (SS), relapse-free (RFS), and progression-free (PFS) survival of patients with renal cell carcinoma (RCC) after NETE.

Materials and methods. The observational study included medical data of 507 patients with RCC and tumor IVC thrombosis operated after NETE. The median volume of blood loss was 4000 [2000–6500] mL. In 312 (61.5%) patients, ARD without a leukocyte filter was used to compensate for blood loss (median volume of reinfused autoerythrocytes – AE was 1140 [700; 1900] mL). Transfusion of DE was required in 387 (76.3%) cases; the median number of DE transfused doses was 3 [1; 5]; 475 (93.7%) patients were discharged from the hospital. The median follow-up of all surviving patients was 24 (1–189) months.

Results. Indications for blood transfusions (DE and AE) were directly correlated to the pN (r=0.101; p=0.024) and pT (r=0.091; p=0.040) categories, respectively. The use of AE had no significant effect on the rate of hemostasis disorders and coagulopathic complications compared to other methods of blood loss replacement: 6.8% (21/311) vs 4.7% (9/193), p=0.227; 5.1% (16/311) vs 4.1% (8/193), p=0.394, respectively. ARD had no effect on SS, RFS (after radical surgery), and PFS (after cytoreductive surgery) after NETE. There was a reduction of SS in patients who received DE transfusions compared with those who did not (hazard ratio 0.4; 95% confidence interval 0.1–0.9; p=0.048). The effects of DE transfusions on RFS and PFS were not identified.

Conclusion. Intraoperative ARD use is an effective and safe method of correcting anemia, which does not increase the risk of coagulopathic complications or decrease survival rates. The non-use of the leukocyte filter during AE preparation does not worsen the medium-term oncological results of RCC surgical treatment with tumor IVC thrombosis. The effect of DE transfusion on the survival of RCC patients after NETE requires further research.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Byrne A, Torrens-Burton A, Sivell S, et al. Early palliative interventions for improving outcomes in people with a primary malignant brain tumour and their carers. Cochrane Database Syst Rev. 2022;1(1):CD013440. DOI: 10.1002/14651858.CD013440.pub2