Vol 25, No 3 (2023)

Literature data and own experience of nutritional support in oncology has been analyzed. Nutritional support is an integral part of the management of cancer patients. Diagnosis of nutritional deficiencies is important, with an accent on early detection of muscle loss and severely malnourished patients. The main methods of nutritional support are oral nutritional supplements, enteral and parenteral nutrition, as well as dietary advice and maintenance of physical activity. Oral nutrition should always be used in the absence of absolute contraindications. The effectiveness and indications of prehabilitation measures require further study, but now it is possible to single out a category of patients in whom they can be fully implemented. It can be cases requiring neoadjuvant chemotherapy.

Aim. Computed tomographic preoperative assessment of sarcopenia in patients with gastric cancer as a part of combined treatment and the study of the relationship between sarcopenia and postoperative complications.

Materials and methods. We analyzed retrospectively the data of 65 patients with morphologically verified diagnosis of stage IIA–IIIC gastric cancer. All patients at stage I of the combined treatment received neoadjuvant chemotherapy (NCT) according to the FLOT regimen, and then a gastrectomy with D2 lymph node dissection was performed. Computed tomography (CT) scans were performed before NCT initiation and 3.5 to 5 weeks after NCT completion for preoperative staging and assessment of tumor response. Using the obtained CT data, CT sarcometry was performed by calculating the cross-sectional area of skeletal muscles at the L_III vertebra level and the “skeletal-muscular index”. Postoperative complications were assessed using the Clavien–Dindo classification. Non-parametric comparison methods were used to assess the significance of differences between groups and subgroups (Wilcoxon T-test, Pearson χ² test). Differences were considered statistically significant at p<0.05.

Results. We analyzed the incidence of sarcopenia in the examined patients before the NCT and immediately before the surgery. Sarcopenia was noted in 41 (63.1%) of 65 patients before NCT and in 50 (76.9%) patients after NCT, which indicates its high prevalence in patients with stomach cancer and the adverse effect of NCT on the muscular status of patients (76.9% versus 63.1%). Postoperative complications were diagnosed in 12 of 65 patients (18.5%). The rate of postoperative complications in patients with and without sarcopenia was not statistically significantly different (p=0.392); however, complications of Clavien–Dindo grade ≥IIIb occurred only in patients with sarcopenia (p<0.001).

Conclusion. According to our data, NCT in gastric cancer aggravates preoperative nutritional disorders. CT, as a standard method of staging and assessing the tumor response to NCT for gastric cancer, provides a tool to assess the state of muscle mass in patients before and after NCT. Preoperative sarcopenia is a risk factor for severe postoperative complications in patients with gastric cancer after gastrectomy.

Ovarian cancer (OC) is a common malignancy of the female reproductive system. In most patients, OC is diagnosed in the later stages, leading to an abysmal prognosis. The standard treatment for OC is surgery and chemotherapy; however, relapse often occurs after treatment, especially in patients with advanced disease. New therapeutic options based on advances in tumor genetics and molecular biology are needed to improve treatment outcomes. Manipulations with genes and the proteins they express, affecting oncogenesis and treatment resistance, seem promising, and proteins and gene fragments identified using molecular methods become valuable markers in the supportive pharmacodiagnosis and tailoring of complex therapy. This article describes the research achievements in genetic markers in OC.

Background. In an era of breakthroughs in cancer immunotherapy, CheckMate 067 studies declared the combination of PD-1 and CTLA-4 inhibitors a new standard of care for patients with metastatic melanoma (MM). A significant limitation of the widespread use of the combination of ipilimumab and nivolumab in routine clinical practice is the high risk of severe immune-mediated adverse events. Prolgolimab and nurulimab are a combination of fixed doses of original monoclonal antibodies (manufactured by JSC "BIOCAD," Russia) to the PD-1 receptor (prolgolimab) and the CTLA-4 receptor (nurulimab) (3:1 ratio). This paper presents the results of an international, multicenter, double-blind, placebo-controlled, comparative, randomized, phase II OBERTON clinical study to investigate the efficacy and safety of nurulimab + prolgolimab combination therapy with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable melanoma (uRM) or MM (NCT03913923).

Materials and methods. The study included patients with uRM or MM who were not previously treated for metastatic disease. The patients were randomized into two groups (1:1). Patients in group 1 were treated with a nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) combination at a dose of 0.2 mL/kg (equivalent to 1 mg/kg of nurulimab and 3 mg/kg of prolgolimab) once every 3 weeks during the first 4 blinded infusions. Patients in group 2 received prolgolimab monotherapy at a dose of 3 mg/kg once every 3 weeks during the first 4 blinded infusions. Starting from infusion 5, patients in both groups received open prolgolimab 1 mg/kg once every 2 weeks. The primary endpoint of the study was progression-free survival (PFS). The study is registered on ClinicalTrials.gov under the number NCT05732805 and is currently ongoing, but recruitment of new patients has been completed.

Results. One hundred seventeen patients were randomized and received at least one dose of the study therapy. At a median follow-up of 16.79 months, the median PFS was 12.2 (4.9; not achieved) months in the nurulimab + prolgolimab group and 2.8 (1.5; 4.7) months in the prolgolimab monotherapy group (95% confidence interval 0.36-0.90, hazard ratio 0.57). PFS at 24 months was 41% in the nurulimab + prolgolimab group and 25.4% in the prolgolimab monotherapy group. In both groups, the therapy was well tolerated. Grade 3-4 immune-mediated adverse events were reported in 15.5% of patients who received nurulimab + prolgolimab, compared with 1.7% of those who received prolgolimab alone. The most frequent grade 3-4 treatment-related adverse events in both treatment groups were increased alanine aminotransferase and aspartate aminotransferase and asthenia. Overall, the safety profile was favorable, as expected for the class of immune checkpoint inhibitors, anti-CTLA-4, and anti-PD-1 monoclonal antibodies.

Discussion. The results demonstrate a favorable safety profile in both the nurulimab + prolgolimab combination and prolgolimab monotherapy groups as the first-line treatment for uRM or MM. The assessment of the primary endpoint, PFS, showed the benefit of combination immunotherapy followed by switching to prolgolimab compared to prolgolimab alone.

Conclusion. Combination immunotherapy with the CTLA-4 inhibitor nurulimab and the PD-1 inhibitor prolgolimab, available as a combination of solutions of two drugs in a single vial, with a further switch to monotherapy with prolgolimab, can fill an important niche in the treatment of patients with uRM or MM. Confirmation of the obtained data on the efficacy and safety of the combined regimen of nurulimab + prolgolimab in comparison with PD-1 inhibitor monotherapy is expected from the ongoing phase III BCD-217-2 OCTAVA study (NCT05732805).

Background. Breast cancer ranks first in the structure of cancer morbidity and mortality. Involvement of a large number of regional lymph nodes is considered a poor prognostic outcome. The mechanisms of development of lymphogenous metastasis in general and common in particular are not fully understood. Integrins are involved in the metastatic process by mediating tumor cell invasion and adhesion to vascular endothelium.

Aim. To study the role of integrins in lymphogenous metastasis.

Materials and methods. The study included 72 patients diagnosed with invasive breast carcinoma of no special type who underwent surgical treatment on the basis of the cancer research institute national research medical center. The average age reached 51.2 years. In accordance with the indications and morphological data, the patients underwent antitumor treatment. The tissue of the primary tumor obtained by trepanbiopsy. Histological and immunohistochemical examination was carried out according to the standard method. In primary tumor cells, the presence or absence of cytoplasmic or membrane/cytoplasmic colocalization of CD61 (Integrin beta 3), CD104 (Integrin beta 4), CD51 (Integrin alpha-V) expression was assessed. When statistically processing the results, Fisher's test and one-way regression analysis were used.

Results. In the N3 group, the frequency of cytoplasmic expression of CD 61 was higher at the trend level (40.9 and 18%; p=0.074). In the group of patients with N3, positive cytoplasmic expression of CD104 (37.5 and 15.0%; p=0.029) and membrane and cytoplasmic colocalization (52.6 and 15.1%; p=0.004) were more often detected. In the group with N1 and N2, membrane and cytoplasmic colocalization of CD104 expression was less common (15.8 and 54.7%; p=0.006). When studying the expression frequency of CD51 integrin, no significant differences were found depending on the severity of lymphogenous metastasis.

Conclusion. Expression of CD104 in primary tumor cells is strongly associated with widespread lymphogenous metastasis. Studies of the role of integrins in the development of lymphogenous metastasis are promising for predicting the prevalence of this process in the preoperative period and for searching for methods of influencing the tumor.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous orphan lymphoproliferative disease with an aggressive course, which accounts for 30–40% of all non-Hodgkin lymphomas. Approximately 3,000 new cases of DLBCL are diagnosed annually in Russia. The trend towards a steady increase in DLBCL incidence worldwide and the rapidly changing treatment landscape with the introduction of innovative options require the updating of epidemiological data. Despite a deeper understanding of the lymphomagenesis and molecular heterogeneity of DLBCL, the R-CHOP regimen remains the first-line standard of care for the vast majority (74%) of patients in Russia and worldwide. The effectiveness of this approach varies greatly and depends on several clinical, biological, and genetic factors. Currently, the most effective and simple prognostic model is the International Prognostic Index (IPI), according to which approximately 20% of patients are at intermediate/high risk of early progression (IPI3-5) and require therapy modification. After the first-line standard immunochemotherapy, 60–70% of DLBCL patients achieve long-term remission with the potential for cure. However, the occurrence of relapse or refractory disease in the remaining 40% of patients is associated with an abysmal prognosis with a median overall survival of about 6 months, which tends to decrease with each subsequent line, warranting an urgent need for new innovative treatments for patients with relapsed DLBCL.

Aim. To reveal and study basic endoscopic differential-significant criteria characterizing gastric-like form of primary non-Hodgkin's lymphoma (NHL) from adenocarcinoma and signet-ring cell carcinoma (SRCC) of the stomach.

Materials and methods. In the prospective study, based of Blokhin National Medical Research Center of Oncology in the period from 2019 to June 2023, 106 patients with gastritic-like forms of primary NHL, adenocarcinoma and SRCC of the stomach were analyzed. Complex endoscopic study included examination in the modes of white light, magnification, narrow-band imaging (NBI, BLI, LCI) was done.

Results. All patients were divided into three groups: MALT gastric lymphoma (38 patients, 35.8%), gastric adenocarcinoma (33 patients, 31.1%), and SRCC (35 patients, 33.1%). At MALT-lymphoma the tumor was localized in the antrum of the stomach (52.6%),adenocarcinoma and SRCC – in the body (45.5 and 60%). In the tumor structure in MALT-lymphoma of the stomach in 100% of cases multiple point areas of microdepressions and multicenter character of the lesion were determined. At adenocarcinoma – depressed area in the central part of tumor (45.5%), at SRCC – extended areas of microdepressions (51.4%) and multicentric character of lesions. At MALT-lymphoma the pit pattern in 63.2% is of "balloon" type, vascular – of tree-like type (84.2%). In adenocarcinoma the vascular pattern was of the loop-type (42.4%), in SRCC – of the corkscrew-type (74.3%). Demarcation line was observed only in adenocarcinoma (100%). At endosonographic study at MALT-lymphoma the tumor was coming from deep layers of mucous coat (100%), changes of regional lymph nodes (LN) were absent, at adenocarcinoma – from mucous membrane (100%), LN were not changed, at SRCC – submucous spread of tumor (100%), changes in LN (40%).

Conclusion. Complex endoscopic examination is necessary to improve the quality of endoscopic examination of malignant gastric-like tumors, to determine the depth of invasion and spread of the tumor process, to assess the regional lymph drainage.

Background. Timely diagnosis and treatment of iron deficiency anemia in cancer patients affect the quality of life and the effectiveness of anti-tumor treatment. However, choosing a method for correcting anemia is imperative to achieve maximum efficiency and safety with the least financial costs.

Aim. To evaluate postoperative methods for treating iron deficiency anemia in patients with gynecological cancers based on a comparative analysis of the clinical and economic outcomes of intravenous iron carboxymaltosate and blood transfusions.

Materials and methods. A study of 125 cases of malignant neoplasms of the female reproductive system with a history of iron deficiency anemia was conducted. Study Group 1 included 85 patients with malignancies receiving 500–1000 mg of iron carboxymaltosate (ICM) intravenously; Group 2 included 40 patients with transfusion of packed red cells (PRC). Clinical and economic outcomes of methods for anemia treatment were analyzed.

Results. In Group 1, the maximum increase in hemoglobin level was observed from Week 2 of ICM treatment (median increase 1.3 g/dL) peaking by Week 9–10 (median increase 2.3 g/dL). In Group 2 the maximum increase in hemoglobin level was noted at Week 1 after PRC transfusion (median increase 2.1 g/dL), with a gradually decreasing hemoglobin level for 3 weeks after that. No side effects of ICM treatment were reported. In 7 (17.5%) patients, a pyrogenic reaction (hyperthermia) was reported after a blood transfusion. The median time from surgery to the beginning of anti-tumor treatment (radiation therapy, chemotherapy) in Group 1 was 19 days [17; 25] vs. 26 days [22; 30] in Group 2 (p=0.0021).

Conclusion. High-dose ICM therapy for iron deficiency anemia in patients with gynecological malignancies is cost-effective and shows a long-term clinical effect.

Background. COVID-19 (COrona VIrus Disease 2019) is a serious threat to cancer patients, who are at an increased risk of severe infection complications. Pre-exposure prophylaxis with a combination of monoclonal antibodies, tixagevimab-cilgavimab (Evusheld), has been shown to be effective in preventing COVID-19, reducing hospital admission rate and mortality in immunocompromised individuals.

Aim. To describe the experience of using tixagevimab-cilgavimab for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapies.

Materials and methods. The retrospective analysis included case histories of 79 patients (57% females and 43% males) with solid tumors treated at the Moscow City Clinical Oncology Hospital No. 1 from October 2022 to June 2023. All patients received tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis.

Results. The mean age was 64±11 years (32 to 83 years). Seventy-three percent of patients received cytotoxic therapy, associated with an increased risk of infectious complications, including COVID-19. No immediate or delayed adverse events related to tixagevimab-cilgavimab were reported. During the observation period since the drug injection, 3 (3.8%) new mild cases of COVID-19 were reported.

Conclusion. Tixagevimab-cilgavimab (Evusheld) is safe and effective for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapy.

Background. Despite high metastatic potential, melanoma rarely metastasizes to the tracheobronchial tree, accounting for 4.5-5.3% of cases. Therefore, epidemiological, clinical, and pathological features, as well as treatment, are based on individual reports in the literature.

Aim. To present a clinical case of isolated endobronchial metastasis of melanoma.

Materials and methods. A 67-year-old patient underwent surgical treatment for stage IIb pT2N0M0 melanoma of the IV toe of the left foot in August 2014. Histological study showed the ulcerated epithelioid cell pigment melanoma of level III invasion according to Clark classification, and the Breslow thickness was 2 mm. No adjuvant treatment was administered.

Results. During the follow-up, no signs of disease progression were found. In December 2022, the patient survived a new coronavirus infection. In February 2023, the patient reported dyspnea on exertion, dry cough, and hemoptysis. Fibrobronchoscopy in the upper lobe of the left lung in one of the subsegmental branches revealed pigmentation of the bronchial mucosa of gray and black in some spots. Based on the results of cytological examination, metastasis of pigment epithelioid cell melanoma was diagnosed. According to imaging studies, no other manifestations of melanoma progression were identified. The patient received immunotherapy with pembrolizumab for 6 months with no signs of metastasis progression.

Conclusion. Isolated endobronchial metastasis of melanoma is uncommon. The latency period in the presented case was 103 months. The clinical presentation included dyspnea during physical exertion, dry cough, and episodes of hemoptysis. The main diagnostic method is fibrobronchoscopy with biopsy for morphological examination. Imaging methods are necessary to establish the spread of the tumor.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database of Systematic Reviews 2023, Issue 5. Art. No.: CD013798. DOI: 10.1002/14651858.CD013798.pub2

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Davenport C, Rai N, Sharma P, Deeks JJ, Berhane S, Mallett S, Saha P, Champaneria R, Bayliss SE, Snell KIE, Sundar S. Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic women. Cochrane Database of Systematic Reviews 2022, Issue 7. Art. No.: CD011964. DOI: 10.1002/14651858.CD011964.pub2. Accessed 12 October 2023.