The role of ultrastaging in sentinel lymph node biopsy with ICG mapping in endometrial cancer

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BACKGROUND

In the United States and Europe, endometrial cancer is the most common malignancy of the female reproductive system. In 80% of cases, the disease is detected at an early stage, which explains the increasing clinical attention to this condition [1–3].

An essential component of staging is the assessment of regional lymph node status, as metastatic involvement is considered the most important prognostic factor and a reliable predictor of tumor recurrence [1].

The 2023 FIGO classification, for the first time, specifies the size of lymphatic metastases, which determines their clinical significance. Thus, lesions larger than 2 mm are defined as macrometastases, those between 0.2 and 2 mm as micrometastases (pN1mi). The concept of isolated tumor cells (ITCs) has been introduced, defined as clusters not exceeding 0.2 mm (pN0i+) or 200 cells [4]. The presence of micrometastases is associated with poor prognosis in patients not receiving adjuvant therapy, whereas ITCs do not appear to significantly affect the outcomes. According to the NCCN guidelines, ITCs in lymph nodes are not considered metastatic involvement [5–7].

The risk of lymphatic metastasis is assessed depending on the depth of myometrial invasion and the tumor histotype. The frequency of lymph node involvement is 4%–6% at low risk, 12%–14.8% at intermediate risk, and may reach 25% or more at high risk [8, 9].

Lymph node status can be determined by two approaches: regional lymphadenectomy or sentinel lymph node biopsy (SLNB).

Over the past decade, SLNB has been recognized as an equally valuable alternative to lymphadenectomy in patients with early-stage endometrial cancer; moreover, pelvic and para-aortic lymphadenectomy has been associated with such complications as lymphocyst formation, lymphedema, hemorrhage, and urological, neurological, and vascular disorders [8–10].

Compared with lymphadenectomy, SLNB is characterized by lower invasiveness while maintaining high sensitivity [11, 12]. According to a meta-analysis by Fan et al., published in 2024 and including data from 62 studies, the sensitivity of SLNB did not differ between patients at low and high risk of lymphatic metastasis [13].

However, the surgical staging approach based on SLNB has sparked discussion within the scientific community regarding the practical implementation of this procedure. The effectiveness of sentinel lymph node detection was studied first, most often using indocyanine green, methylene blue, and technetium⁹⁹. Numerous studies have demonstrated no difference in sentinel lymph nodes detection rates when using indocyanine green and methylene blue, whereas technetium⁹⁹ was identified as one of the factors contributing to false-negative SLNB results according to the meta-analysis by Fan et al. (2024) [13, 14]. It should be acknowledged, however, that the technical infrastructure and practical experience in sentinel lymph node detection may also play a role. For example, a group of authors from Tomsk reported high effectiveness of sentinel lymph node detection when using technetium⁹⁹ [15].

The second key aspect of the SLNB concept concerns the choice of methods for the morphological assessment of lymph nodes, which are generally divided into intraoperative and postoperative approaches. Initially, preference was given to intraoperative methods, given the possibility of immediate adjustment of the surgical plan—that is, extending the procedure from SLNB to lymphadenectomy in the event of metastatic involvement. The available options included frozen-section histological examination and intraoperative cytological assessment.

Frozen-section examination of sentinel lymph nodes has largely lost its relevance due to low sensitivity; however, it is still recommended by the most authoritative societies when suspicious lymph nodes are detected intraoperatively [16–18].

Intraoperative cytological assessment, in most cases, does not allow the detection of micrometastases, but it is effective for identifying macrometastases, since in frozen-section histology tumor cells do not always happen to be present in the plane of the section [19]. At the same time, a Russian group of authors from Tomsk has reported that this method of assessment is useful in surgery planning [15].

The 2024 meta-analysis by Ahuja et al. showed that, although the sensitivity of routine histological examination was higher for micrometastases, cytological evaluation of lymph nodes was recognized as a rapid and low-cost method that can be used when no alternative is available. Along with the advantages and disadvantages of intraoperative cytological and histological assessments, prolongation of surgery time should be considered, which is not always economically justified [20].

One of the approaches to postoperative histological examination of sentinel lymph nodes is standard hematoxylin and eosin (H&E) staining, performed on two sections per node, and ultrastaging. The scientific data describes several methods of paraffin block preparation, sectioning intervals, the number of sections, and staining techniques. Authors from Memorial Sloan Kettering Cancer Center reported that the lymph node is sliced along its long axis, and two blocks are prepared, each yielding three slides at 50 µm intervals: one stained with H&E, one with cytokeratin, and one reserved as a control. Although the authors did not specify the total number of slides prepared, they noted that using a single cytokeratin-stained immunohistochemical (IHC) slide per block provided better detection of metastatic involvement compared with a greater number of IHC slides [21].

The current 2025 NCCN protocol recommends preparing serial sections of the lymph node, without specifying the interval between them, using H&E staining with or without additional immunohistochemical markers.

In the study by Clark et al., published in 2024, the authors proposed the following ultrastaging protocol: the lymph node was embedded into a paraffin block and sectioned perpendicular to its long axis at 2 mm intervals, followed by four 5-µm sections cut at 50 µm intervals. Three slides were stained with H&E, and the fourth with cytokeratin. The authors did not specify what was done with the remaining portion of the block, but it is evident that with this method of histological specimen preparation, a substantial part of the lymph node remains unexamined. Compared with protocols using two IHC slides, this method was associated with a 0%–0.9% increase in the likelihood of false-negative results, whereas reducing economic costs by approximately twofold [22].

Ultrastaging protocols by other investigators described sectioning the lymph node either along or perpendicular to the long axis, with section thickness ranging from 50 to 250 µm, sometimes alternating H&E staining with cytokeratin IHC and preparing 2–3 slides. Recent studies indicate that the optimal balance between diagnostic yield and cost-effectiveness is achieved with a single IHC cytokeratin-stained slide per block [23–26].

Thus, based on the scientific data, it can be concluded that the success of the procedure depends not so much on the use of immunohistochemistry as on the method of preparing the histological specimen as such. Nevertheless, the effectiveness of detection in routine practice, the selection of patient groups for this stage, and the choice of sentinel node assessment protocols remain highly variable, and the investigation into the most effective approaches provides substantial scientific and practical benefit.

AIM

The study aimed to evaluate the feasibility and optimal approach for ultrastaging of sentinel lymph nodes after indocyanine green (ICG) mapping across different risk groups for lymphatic metastasis in stage 1 endometrial cancer.

METHODS

Study Design

A retrospective cohort study was conducted, including patients aged 60–73 years with histologically confirmed stage 1 endometrial cancer.

Eligibility Criteria

Inclusion criteria:

• Histologically verified stage 1 endometrial cancer;
• Available ICG mapping of sentinel lymph nodes;
• ECOG performance status of 0–2;
• Age >60 and <73 years.

Non-inclusion criteria:

• Decompensated somatic diseases;
• History of allergic reactions to indocyanine green or iodine;
• Hyperthyroidism.

Study Setting and Duration

The study was conducted at Department of Oncogynecology No. 70, Moscow Botkin Multidisciplinary Scientific and Clinical Center (MBMSCC), Department of Health of Moscow, and at the Kaluga Regional Clinical Oncology Center (KRCOC) between January 2023 and December 2024.

Research Methodology

A total of 286 patients with endometrial cancer stages cT1a–T1bN0M0 were included in the study and divided into three groups according to the risk of lymphatic metastasis:

• Group 1, low risk (n = 173);
• Group 2, intermediate risk (n = 80);
• Group 3, high risk (n = 33).

The FIGO (2009) classification was used for disease staging, taking into account the depth of myometrial invasion, histological type, tumor grade, and lymph node status.

Indocyanine green was used as the fluorescent dye. Prior to surgery, 1 mL of the agent diluted in 4 mL of sterile water for injection was injected submucosally into the cervical stroma at the 3- and 9-o’clock positions (see Fig. 1).

 

Fig. 1. The scheme of preparation of the preparation for ultrastading: IHC, immunohistochemical study; ITCs, isolated tumor cells; H&E, hematoxylin and eosin.

 

During laparoscopic procedures, sentinel lymph node biopsy was performed following ICG mapping. The excised sentinel lymph nodes underwent standard histological examination with H&E staining. If metastases were detected, the examination was concluded; if none were found, ultrastaging was performed with serial analysis of 5–10 sections of the lymph node using immunohistochemical markers for cytokeratin.

For micropreparation, lymph nodes were sectioned at 2 mm intervals, fixed in paraffin blocks, and then cut into 3–5 μm sections at 250 μm intervals. Histological slides were stained with H&E, and immunohistochemistry was performed on every other section.

Sections were deparaffinized and rehydrated in xylene and graded alcohols. Antigen retrieval was performed using a PT-Link Thermo system. Immunohistochemical (IHC) testing was conducted on a Ventana Benchmark Ultra automated stainer (Ventana Medical Systems, USA) with Ventana reagents and a CK8/18 DO-7 Mouse Monoclonal Dako (Agilent Dako, Denmark), using the OptiView DAB IHC Detection Kit (Company MAXXmarketing GmbH, Germany) for visualization.

Microscopy was performed with a Zeiss Axiolab microscope (Zeiss, Germany); the presence of membranous staining of cells was interpreted as evidence of adenocarcinoma metastasis. The evaluation was independently performed by two pathologists.

Main Study Outcome

The main outcomes were the detection rates of metastatic involvement of sentinel lymph nodes based on standard histological examination and microstaging with IHC.

Ethics Approval

The study was approved by the Local Ethics Committee of the Russian Medical Academy of Continuous Professional Education (Protocol No. 3 dated February 22, 2022).

Statistical Analysis

Sample Size Calculation

The sample size was not pre-calculated.

Methods of Statistical Data Analysis

Descriptive statistical methods were used, and analyses were performed with the Medstatistic platform (https://medstatistic.ru/), in particular, Pearson’s chi-square test using 2×2 contingency tables. Results were considered statistically significant at p ≤ 0.05.

RESULTS 

Participants

The study included 286 patients with an ECOG performance status of 0–2 (see Table 1).

 

Table 1. Characteristics of patients

Parameter	Value
Total number of patients	286
Age, years (M ± SD, range)	66.2 ± 3.8 (60–73)
TNM disease stage	cT1a: 198 (69.2%) cT1b: 88 (30.8%)

 

Primary Results

ICG mapping of sentinel lymph nodes was performed in 286 patients with confirmed endometrial cancer. Following preoperative evaluation, patients were stratified by the risk of lymphatic metastasis (see Table 2). The difference between the groups was that at the KRCOC, SLNB was performed in all patients as part of the study, whereas at the MBMSCC, in cases of intermediate and high risk, SLNB replaced LAE only in the presence of significant comorbidities. Thus, the MBMSCC cohort was predominantly composed of low-risk patients.

 

Table 2. Distribution of patients into groups depending on the risk of lymphogenous metastasis, n (%)

Parameter	MBMSCC	KRCOC	Total
Number of patients, n	94	192	286
Risk of lymphatic metastasis: low intermediate high	67 (71.3) 22 (23.4) 5 (5.3)	106 (55.2) 58 (30.2) 28 (14.5)	173 (60.5) 80 (28) 33 (11.5)

Note: MBMSCC, Moscow Botkin Multidisciplinary Scientific and Clinical Center; KRCOC, Kaluga Regional Clinical Oncology Center.

 

In both institutions, low-risk patients prevailed, although their proportion was somewhat higher at MBMSCC. In the intermediate-risk group, no significant differences were observed (p = 0.229); moreover, these patients represented a considerable share of the overall cohort. Considering a bigger proportion of high-risk patients in KRCOC than in MBMSCC (14.5% vs. 5.3%), it can be stated that nearly one-third of high-risk patients present with comorbidities limiting the feasibility of complete lymphadenectomy. Thus, incorporating SLNB into the surgical armamentarium represents a significant element of routine clinical practice. At MBMSCC, SLNB was performed in high-risk patients only in cases of comorbidities (n = 5), whereas at KRCOC this procedure was completed in all patients.

In all cases, sentinel lymph node detection rates were assessed during SLNB. The results of this stage are presented in Table 3.

 

Table 3. Sentinel lymph node detection efficiency, n (%)

Parameter	MBMSCC	KRCOC	Total
Number of patients, n	94	192	286
Detection pattern: bilateral unilateral	66 (70.2) 17 (18.1)	137 (71.4) 49 (25.5)	203 (70.9) 66 (23.8)
No detection	11 (11.7)	6 (3.1)	17 (5.9)
Any detection achieved	83 (88.3)	186 (95.9)	269 (94.1)

Note: MBMSCC, Moscow Botkin Multidisciplinary Scientific and Clinical Center; KRCOC, Kaluga Regional Clinical Oncology Center.

 

In the KRCOC group, unilateral detection was somewhat more successful, resulting in a higher overall number of sentinel lymph nodes identified (n = 137). The absence of sentinel lymph node staining was observed considerably less often among KRCOC patients (n = 6). This may be attributable to the stage of methodological adoption at the MBMSCC. However, the rates of bilateral detection were comparable, indicating that the technique is highly reproducible (p = 0.816).

In low-risk patients, no additional procedures were undertaken when sentinel lymph nodes failed to stain, and the intervention was limited to hysterectomy. In patients from the intermediate- and high-risk groups, the absence of sentinel lymph node staining was managed by performing pelvic lymphadenectomy on the corresponding side, or bilaterally (in cases of absent detection on both sides).

The sentinel lymph nodes were submitted for pathological examination, the results of which are presented in Table 4.

 

Table 4. Results of detection of macro- and micrometastases during morphological diagnostics

Parameter	MBMSCC			KRCOC			Total
Number of patients with successful detection, n	83			186			269
Type of involvement	macro	micro	total	macro	micro	total	macro	micro	total
Risk of lymphatic metastasis, n (%): low	0	2 из 58 (3.4)	2 из 58 (3.4)	1 из 106 (0.9)	3 из 106 (2.8)	4 из 106 (3.8)	1 из 164 (0.6)	5 из 164 (3)	6 из 164 (3.6)
intermediate	2 из 20 (10)	1 из 20 (5)	3 из 20 (15)	3 из 58 (5.2)	4 из 58 (6.9)	7 из 58 (12.1)	5 из 78 (6.4)	5 из 78 (6.4)	10 из 78 (12.8)
high	2 из 5 (40)	0	2 из 5 (40)	4 из 28 (14.3)	1 из 28 (3.6)	5 из 28 (17.9)	6 из 33 (18.2)	1 из 33 (3.1)	7 из 33 (21.3)

Note: MBMSCC, Moscow Botkin Multidisciplinary Scientific and Clinical Center; KRCOC, Kaluga Regional Clinical Oncology center; micro, micrometastases; macro, macrometastases.

 

No significant differences were found between the MBMSCC and KRCOC cohorts in the frequency of N1 detection (p = 0.964). It should be noted that the higher proportion of N1 detection in the high-risk group at MBMSCC was most likely due to the small number of patients in this group. In contrast, only 6 metastatic lymph nodes were identified in the low-risk group: 5 cases of micrometastases and 1 case of macrometastases. In the intermediate-risk group, 5 micrometastases and 5 macrometastases were detected. In the high-risk group, 1 micrometastasis and 6 macrometastases were found.

In total, 23 metastatic lesions were detected in the study, including 12 macrometastases (52.2%) and 11 micrometastases (47.8%) (see Table 4).

The ratio of macrometastases to micrometastases is presented graphically in Fig. 2. Percentages indicate the proportions of macro- and micrometastases according to the above data.

 

Fig. 2. The ratio of the N1 fractions detected during the morphological diagnosis. The green scale corresponds to the proportion of micrometastases, and the yellow scale corresponds to macrometastases.

 

Fig. 2 clearly demonstrates an increase in the frequency of macrometastases and a decrease in the proportion of micrometastases from the low to the high risk.

Pooling data from the two clinics makes it possible to identify patterns in SLNB outcomes among patients with a low expected risk of metastasis. Nevertheless, in absolute numbers, the distribution across groups amounted to 6 cases of N1 in the low-risk group, 10 in the intermediate-risk group, and 7 in the high-risk group. These figures clearly illustrate the importance of surgical staging in each risk group.

To precisely evaluate the characteristics of morphological lymph node diagnostics among patients at the MBMSCC, the contribution of each stage of the pathologists’ work was assessed (see Table 5).

In total, 7 cases of N1 and 4 cases of isolated tumor cells (ITCs) were identified at the MBMSCC (see Table 5).

Of the 11 cases of tumor involvement detected in the lymph nodes, 4 were macrometastases, 3 were micrometastases, and 4 were clusters of ITCs. Among them, standard histological examination identified 3 macrometastases, accounting for 42.9% of all metastatic findings excluding ITCs. Ultrastaging enabled the detection of additional 2 micrometastases, which represented 28.6%. IHC revealed 2 more metastases, including one macrometastasis that at early stages had been interpreted as histiocytosis and one micrometastasis measuring approximately 0.2 mm. In 4 cases, IHC detected isolated tumor cells that lacked clinical significance but represented 36.4% of all lymph node changes (see Fig. 3).

 

Fig. 3. Revealed changes in lymph nodes among patients of the Moscow Multidisciplinary Scientific and Clinical Center named after S.P. Botkin: IHC, immunohistochemical study, ITCs, isolated tumor cells.

 

The analysis of diagnostic value across the stages of morphological examination, as noted above, showed that IHC identified metastatic changes in only 2 of 7 patients, i.e., 28.6%. Recent studies on ultrastaging techniques indicate that preparing a single IHC slide per block may reduce costs while maintaining diagnostic value. The findings of our study confirm this statement.

However, the entire ultrastaging procedure, including lymph node sectioning technique and IHC, led to the detection of 4 out of 7 N1 cases, accounting for 57.1%, underscoring the high importance of all stages of morphological evaluation.

DISCUSSION

According to the data from both participating institutions, the bilateral detection rate of sentinel lymph nodes with ICG mapping was 70.9%. This rate likely has potential for improvement, as a recent publication from colleagues in Moscow reported achieving 91% bilateral detection [27].

The frequency of metastatic involvement in lymph nodes at the corresponding risk level was similar in both clinics. This consistency supports the good reproducibility and reliability of the method for disease staging. Moreover, the similarity extended not only to the overall incidence of N1 cases but also to the ratio of macrometastatic to micrometastatic involvement (see Table 4).

A clear trend was observed toward a decreasing proportion of micrometastases with increasing risk from low to high (see Fig. 2). These findings highlight the clinical characteristics of the disease in terms of the relevance of lymphadenectomy in the high-risk group, where macrometastases predominated, and the adequacy of SLNB in the low- and intermediate-risk groups, where their proportion was substantially lower.

According to the 2024 meta-analysis by Fan et al., combining SLNB with ultrastaging significantly reduces the rate of false-negative results in determining N0/1 status and increases sensitivity [13]. Our results support this conclusion: more than half of the metastatic changes among patients at the MBMSCC were identified through ultrastaging with IHC. However, the authors of recent studies on lymph node morphological assessment techniques have concluded that the process costs may be cut significantly by preparing only a single IHC slide per block, without loss of diagnostic value [23–26]. The present study established that only two out of seven alterations were detected by IHC, and in one case this was a macrometastasis that occupied the major part of the microscopic field and, with high probability, would have been captured in an IHC section. This observation suggests that the significance of IHC may have been somewhat overestimated in earlier publications, and at present the preparation of a single IHC slide per block appears sufficient (see Fig. 4).

 

Fig. 4. The proposed algorithm for optimizing the diagnostic value and economic costs of ultrastiding: IHC, immunohistochemical study; H&E, hematoxylin and eosin.

 

However, metastatic involvement in 3 of 7 cases was detected by standard histological examination (see Fig. 3). This underscores the clear necessity of complementing standard morphology with ultrastaging.

Among the approaches to preparing histological specimens for microstaging, there is considerable variation in the intervals between sections, ranging from 50 to 250 µm. Given that clinical relevance of metastases starts when their size reaches about 200 µm, it appears reasonable to maintain sectioning intervals close to this threshold, at approximately 250 µm.

The economic aspect of SLNB also deserves attention. The algorithm entails substantial costs associated with technical support, fluorescent dyes, and time resources. In the absence of an ultrastaging step, the remaining expenditures are not justified due to the low sensitivity of standard histological examination. Thus, it can be concluded that performing SLNB without subsequent ultrastaging is not expedient, even from an economic perspective.

Therefore, based on the present study evaluating the significance of SLNB with microstaging in patients across different risk groups for lymphatic metastasis, the following conclusions can be drawn.

• This procedure is critically important in the low-risk group, where the overall rate of N1 detection was 3.6%, whereas according to the scientific data, the frequency of N1 detection reaches 4%–6% [8, 9]. This suggests that the potential of the method has not yet been exhausted and that further refinement of the SLNB technique with ultrastaging may enable the identification of a greater number of SLN lesions. All N1 cases in the MBMSCC cohort were identified during ultrastaging, with one of the two cases detected by IHC. In the overall macrometastasis to micrometastasis ratio across the combined cohort of both clinics, the proportion of micrometastases in the low-risk group reached 83.3%. This underscores the relevance of SLNB with ultrastaging in the low-risk population. It should also be noted that this cohort was the most numerous, accounting for approximately 60% of the patients. Given this patient distribution, ommitting SLNB with ultrastaging would result in a paradox: treatment in the low-risk group would be limited to hysterectomy alone, whereas patients at intermediate and high risk would undergo staging. Consequently, the cohort of low-risk patients with N1 disease, including micrometastases, would not receive adjuvant therapy. Thus, the low-risk group would be underestimated, which could account for a substantial number of recurrences. Indeed, according to published data, recurrence-free survival at stages 1–2 reaches 90%, whereas in the presence of metastases this rate drops to only 48% [28].
• In the intermediate-risk group at the MBMSCC, of the three N1 cases, one metastasis was identified by standard histological examination, one by ultrastaging with H&E staining, and one by IHC. In the latter case, the lesion was a macrometastasis that could be differentiated from histiocytosis only through IHC. This underscores the importance of each stage of morphological diagnostics for patients in this group. Across all patients included in the study, the frequency of N1 detection was 12.8%, which is comparable to the scientific data, where authors report 12%–14.8% [8, 9]. Thus, in terms of diagnostic sensitivity, the method may serve as an alternative to lymphadenectomy in such patients. It should be noted that the number of N1 cases was the highest precisely in the intermediate-risk group, which clearly emphasizes the need for surgical staging in these patients.
• In the high-risk group at the MBMSCC, both lymphatic metastases were identified by standard histological examination. On the one hand, this might suggest that additional morphological examination steps are unnecessary, particularly given that nearly all detected N1 cases were macrometastases and that adjuvant therapy in these patients is most often determined by tumor grade or depth of invasion. On the other hand, the group is relatively small, and performing all stages in those patients without metastases on standard histology would not entail substantial economic costs. Moreover, adjuvant treatment regimens are, without a doubt, influenced by lymph node status. Therefore, SLNB with ultrastaging can be considered adequate in this group as well.

There is a growing body of objective evidence for the debate over performing SLNB instead of lymphadenectomy in the high-risk group. With the release of the new 2023 FIGO endometrial cancer classification, 23% of patients previously staged as stage 1 will be reassigned to stage 2, which definitively determines the surgical approach—namely, full lymphadenectomy. At the same time, our study demonstrates that SLNB remains a relevant alternative to lymphadenectomy, particularly in patients with significant comorbidities [29].

Study Limitations

The limitations of this study include its retrospective design and the two-center cohort, which restrict the generalizability of the findings, as well as the imbalance among risk subgroups, particularly the small number of high-risk patients. The absence of randomization and a control group, along with the potential impact of the learning curve in performing ICG mapping and ultrastaging, may have led to biased results. Furthermore, the follow-up period was limited, preventing the assessment of long-term oncologic outcomes and the clinical significance of micrometastases.

CONCLUSION

For patients with stage 1 endometrial cancer, SLNB with ultrastaging should be considered appropriate, except in those at high risk of lymphatic metastasis, who, according to the new FIGO 2023 classification, are reclassified as stage 2. For these patients, this staging option remains relevant in the presence of significant comorbidities.

Immunohistochemical examination plays an important role in ultrastaging; however, the preparation of numerous IHC sections appears impractical. At the same time, 28.3% of metastatic lesions in our study were identified solely by IHC, which clearly underscores the necessity of including at least one IHC slide per block. For the preparation of specimens for ultrastaging, lymph nodes should be sectioned for paraffin blocking in a specific manner, namely perpendicular to the long axis at 2 mm intervals, followed by block preparation with a step of 250 μm. The choice of this technique for preparing histological specimens is justified by the size of clinically significant metastatic lesions.

ADDITIONAL INFORMATION

Author contributions: V.A. Alimov: conceptualization, methodology, data curation, formal analysis, writing—original draft; E.G. Novikova: conceptualization, methodology, writing—review & editing; S.A. Skugarev: data curation, formal analysis, methodology; S.S. Lebedev, Z.A. Bagateliya: writing—review & editing; A.A. Laevskaya, A.M. Arutyunyan: writing—review & editing; D.S. Lantsov, I.O. Tinkova: methodology. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The study was approved by the Local Ethics Committee of the Russian Medical Academy of Continuous Professional Education (Protocol No. 3 dated February 22, 2022).

Funding source: No funding.

Disclosure of interests: The authors have no relationships, activities or interests for the last three years related with for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: In creating this work, the authors did not use previously published information (text, illustrations, data).

Data availability statement: The editorial policy regarding data sharing does not apply to this work, and no new data was collected or created.

Generative AI: Generative AI technologies were not used for this article creation.

Provenance and peer-review: This paper was submitted to the journal on an unsolicited basis and reviewed according to the usual procedure. Two external reviewers, a member of the editorial board, and the scientific editor of the publication participated in the review.

About the authors

Vladimir A. Alimov

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center; Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: alimovvladimirr@gmail.com
ORCID iD: 0000-0002-6423-3917
SPIN-code: 6262-0720

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; Moscow

Sergei A. Skugarev

Kaluga Regional Clinical Oncology Center

Email: saskugarev@yandex.ru
Russian Federation, Kaluga

Elena G. Novikova

Hertsen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Centre

Email: egnov@bk.ru
ORCID iD: 0000-0003-2768-5698
SPIN-code: 2143-9975

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Sergei S. Lebedev

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center; Russian Medical Academy of Continuous Professional Education

Email: lebedevssd@yandex.ru
ORCID iD: 0000-0001-5366-1281
SPIN-code: 2736-0683

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; Moscow

Zurab A. Bagatelia

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center; Russian Medical Academy of Continuous Professional Education

Email: bagateliaz@mail.ru
ORCID iD: 0000-0001-5699-3695
SPIN-code: 5391-5670

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; Moscow

Anastasia A. Laevskaya

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center

Email: ayaksveal@yandex.ru
Russian Federation, Moscow

Anna M. Arutyunyan

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center

Email: dr.arutyunyana@gmail.com
SPIN-code: 3661-8562

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Dmitriy S. Lantsov

Kaluga Regional Clinical Oncology Center

Email: lantsov@mail.ru
ORCID iD: 0009-0001-7314-4844
SPIN-code: 9788-9119

MD, Cand. Sci. (Medicine)

Russian Federation, Kaluga

Irina O. Tinkova

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center

Email: tinkovairen74@yandex.ru
ORCID iD: 0000-0002-6960-1184
SPIN-code: 2410-7520

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Alexey V. Shabunin

Moscow S.P. Botkin Multidisciplinary Research and Clinical Center; Russian Medical Academy of Continuous Professional Education

Email: glavbotkin@zdrav.mos.ru
ORCID iD: 0000-0002-4230-8033
SPIN-code: 8917-7732

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; Moscow

References

Supplementary files