Voprosy onkologii

Introductory Remarks, Doctor of Medical Sciences, Novik A.V.

Alexey V. Novik — 2025-09-11

Joint Analysis of the Interferon Gene Signatures and Cancer-Testis Gene Expression in Cutaneous Melanoma Patients

Aleksei Novik — 2025-09-11

Introduction. Cutaneous melanoma currently lacks well-established molecular biomarkers for predicting immunotherapy response. Emerging candidates under investigation include interferon-stimulated gene (ISG) signatures and cancer-testis antigen (CTA) expression profiles.

Aim. The study performed to characterize the interplay between ISG signatures and CTA expression patterns in cutaneous melanoma patients.

Materials and Methods. The study utilized normalized whole-genome sequencing data comprising expression levels of 43,000 genes from 457 cutaneous melanoma patients, sourced from the publicly available University of California Santa Cruz (UCSC) dataset. Our analysis focused on rhabdoid-testicular CTA genes (n = 186) and interferon-dependent ISG genes (n = 66), the latter analyzed as both full and brief signatures. We performed agglomerative hierarchical clustering via Ward's method separately for ISG and CTA groups. Statistical evaluation of cluster interactions employed seven complementary measures: Pearson's chi-square test, lambda coefficient, contingency coefficient, phi coefficient, Goodman and Kruskal's tau, uncertainty coefficient, and column proportion analysis.

Results. Analysis revealed four conserved ISG clusters across both datasets (two demonstrating high gene expression and two with low expression) showing strong correlation (λ = 0.666, p < 0.0001). For CTA genes, hierarchical clustering identified six primary clusters (two each of high, medium, and low expression genes) at the first level, which further differentiated into ten subclusters at the third clustering level. Initial comparison of first-level ISG and CTA clusters showed no significant association (p > 0.1). Evaluation of third-level CTA clusters against the brief ISG signature demonstrated a weak relationship (symmetric uncertainty coefficient = 0.031, p = 0.003). Only two third-level CTA clusters exhibited meaningful associations with ISG patterns: one characterized by minimal CTA expression coupled with high ISG activity, and another showing the inverse relationship of elevated CTA expression paired with low ISG signature.

Conclusion. This study confirms our prior findings regarding the heterogeneous expression profile of CTA in cutaneous melanoma. The majority of CTA clusters demonstrated no significant association with ISG signatures. The identification of specific CTA-ISG expression patterns as predictive biomarkers for immunotherapy response in melanoma patients warrants deeper investigation.

Differential Diagnostics of Soft Tissue Sarcoma Recurrence and Postoperative Changes: A Comparative Efficacy of Contrast-Enhanced Ultrasound versus Magnetic Resonance Imaging

Elvira S. Lyubimskaya — 2025-09-11

Introduction. Soft tissue sarcomas (STS) present a considerable clinical challenge due to their high risk of local recurrence (LR) and the absence of standardized surveillance protocols. Although MRI remains the gold standard for diagnosis, its utility is limited by high costs and reduced diagnostic accuracy in patients following radiation therapy. Contrast-enhanced ultrasound (CEUS), which demonstrates greater accuracy than conventional ultrasound, represents a promising alternative.

Aim. To evaluate the diagnostic performance of CEUS compared to MRI in differentiating postoperative changes from LR diagnostics.

Materials and Methods. This study included 43 patients with suspected LR who underwent both CEUS and MRI. Histopathological analysis served as the reference standard. Statistical analyses were conducted using specialized software packages, with a significance threshold set at p < 0.05. Diagnostic performance metrics were calculated, and receiver operating characteristic (ROC) curves were generated.

Results. We identified statistically significant (p < 0.05) ultrasonographic and MRI criteria for distinguishing LR from postoperative changes (PO). LR was characterized by structural inclusions with hyperechoic halos, hypervascular or mixed flow patterns, and spiral-shaped contrast enhancement (CE) with type 3 kinetic curves. Conversely, PO typically demonstrated homogeneous hyperechoic structure, cystic components, avascularity, and absence of contrast enhancement without kinetic curves. Notably, lesion location, shape, margins, and stiffness showed no diagnostic value for differentiating LR from PO (p > 0.05). MRI findings further revealed that LR predominantly presented as solid or cystic-solid structures with necrotic areas and exhibited pronounced, heterogeneous CE. PO, however, was characterized by fluid-filled structures, fibrosis, anatomical connections to vascular or bony structures, and weak linear or homogeneous CE (p < 0.05). Diagnostic performance metrics demonstrated high accuracy for both modalities: CEUS achieved 90.0 % sensitivity, 92.3 % specificity, and an AUC of 0.911, while MRI showed 93.3 % sensitivity, 92.3 % specificity, and an AUC of 0.928.

Conclusion. CEUS and MRI should be regarded as complementary rather than competing modalities. Their strategic integration, guided by clinical context and resource availability, facilitates optimal LR detection. Continued technical refinement of ultrasound methodologies and accumulation of clinical experience will further optimize surveillance protocols, enabling earlier LR detection and improving patient prognosis.

The Autologous CaTeVac Dendritic Cell Vaccine in Patients with Melanoma: Final Results of the DENDRON-01 Study

Tatiana Lenidovna Nekhaeva — 2025-09-11

Introduction. Immunotherapy has demonstrated high efficacy in the treatment of melanoma, particularly with the advent of immune checkpoint inhibitors (ICIs). However, systemic immune activation often triggers severe immune-related adverse events (irAEs) that can substantially compromise patient quality of life — a critical concern in adjuvant settings where extended treatment durations are required. In this context, the development of novel, safer, and more targeted immunotherapeutic strategies for melanoma is of paramount importance.

Aim. To evaluate the efficacy and safety of an autologous dendritic cell vaccine (DCV) CaTeVac in melanoma patients, assessing its performance both as adjuvant therapy and standalone treatment in comparison with conventional therapeutic approaches.

Materials and Methods. The study enrolled 154 patients with histologically confirmed melanoma who received DCV treatment between 2009 and 2023. Patients were treated in adjuvant (76 %) or therapeutic (24 %) settings. Adjuvant therapy was administered following complete cytoreduction in stage II–IV patients with high recurrence risk. Therapeutic DCV was reserved for patients with measurable disease who had exhausted standard treatment options. The endpoints included overall survival (OS), progression-free survival (PFS), and the frequency and severity of adverse events, evaluated in comparison with a historical control group.

Results. In the adjuvant setting, administration of the CaTeVac DCV led to a statistically significant improvement in median PFS (15.0 vs. 8.6 months in controls (p < 0.02). The median OS in the CaTeVac cohort remained unreached after more than 10 years of follow-up vs. 52.5 months for controls (p = 0.01). For patients receiving standalone treatment, CaTeVac showed modest but statistically superior PFS versus monochemotherapy (2.5 vs. 2.3 months; p < 0.05), though no significant OS difference was observed (12.4 vs. 11.4 months; p > 0.05). The safety profile of CaTeVac was favorable, with 64 % of treatment cycles being adverse event-free. Fever occurred in 45.1 % of the therapy cycles: grade 1 (40.8 %), 2 (4 %), and 3 (0.3 %). Pain, allergic reactions, local reactions, and laboratory abnormalities each occurred in < 5 % of cycles.

Conclusion. The CaTeVac dendritic cell vaccine demonstrates both clinical efficacy and an excellent safety profile, establishing it as a promising therapeutic option for adjuvant melanoma treatment. In the standalone setting, CaTeVac outperformed conventional monochemotherapy in advanced-stage disease and may serve as a component of personalized immunotherapy in further clinical studies.

Altered Peripheral Blood T-Helper Cell Maturation and Polarization in Primary Skin Melanoma

Ekaterina Prochorovna Kisseleva — 2025-09-11

Introduction. CD4+ T lymphocytes play a key role in immune regulation and are crucial for antitumor defense. They constitute a heterogeneous population that necessitates selective analysis of individual subsets.
Aim. To study the maturation and subset composition of peripheral blood CD4+ T lymphocytes in patients with inoperable cutaneous melanoma compared to healthy controls.
Materials and Methods. The study included 37 patients with disseminated or locally advanced unresectable cutaneous melanoma. Age- and sex-matched healthy donors were enrolled as controls. Multicolor flow cytometry was performed on peripheral blood samples to identify CD3+CD4+ lymphocyte subsets (Th): Th1, Th2, Th17, Tfh, as well as central memory (Th CM) and effector memory (Th EM) cells. Within the total EM and CM cell populations, we conducted detailed analysis of specific Th17 subsets ("classical" Th17, Th17.1, DN Th17 and DP Th17) and Tfh cell populations (Tfh1, Tfh2, Tfh17 and DP Tfh).
Results. While no quantitative changes were observed in the total pool of peripheral blood CD4+ T lymphocytes in cutaneous melanoma patients, we identified significant imbalances in specific subsets, including Th1/Th2 ratios among total CD4+ T lymphocytes, as well as within Th EM and Th CM populations. Furthermore, increased frequencies of memory Th CM and Th EM cells were detected. Shifts in the balance of individual Th17 EM and Tfh EM subsets were also observed. Disease severity correlated with several immunological parameters: elevated Th17 cell counts, decreased Tfh CM lymphocytes, altered ratios between memory cell subpopulations (naive Th and Th EM), and changes in Th17 CM subsets ("classical" Th17 and Th17.1). Collectively, these findings demonstrate an active immune response in melanoma patients involving both cellular immunity (Th1, Th2 and Th17 alterations) and humoral immunity (Tfh subset variations).
Conclusion. Analysis of individual CD4+ T lymphocyte subsets in peripheral blood from cutaneous melanoma patients provides more clinically relevant information than evaluation of the total heterogeneous cell population. Several of the identified parameters may serve as potential biomarkers for predicting disease outcomes or monitoring therapeutic efficacy

Introductory Remarks by Corresponding Member of the Russian Academy of Sciences, Professor Vladimir F. Semiglazov

Vladimir F. Semiglazov — 2025-06-30

Expert Consensus Statement: Sonidegib for the Treatment of Locally Advanced Basal Cell Carcinoma

Кристина Вячеславовна Орлова — 2025-09-11

On May 15, 2025, an Expert Council convened to discuss Therapeutic Options for Locally Advanced Basal Cell Carcinoma with Sonidegib, culminating in a consensus resolution. The resolution outlined key recommendations regarding contemporary systemic therapy approaches for locally advanced basal cell carcinoma.

Special Histological Types of Breast Cancer. Unfavorable Prognosis

Asel G. Kudaibergenova — 2025-06-30

This article continues the discussion on special types of breast cancer (BC), a disease whose history spans millennia. Modern oncology recognizes BC as a heterogeneous group of diseases with distinct morphological features, molecular subtypes, and clinical behavior. Advances in diagnostics and personalized therapy have significantly reduced BC mortality compared to more aggressive malignancies, such as pancreatic or liver cancer.

The second part of this publication focuses on rare and special histological subtypes of BC with unfavorable or uncertain prognosis. The classification of these forms is based not only on morphology but also on immunohistochemical, molecular, and prognostic characteristics, reflecting contemporary clinical approaches.

A study conducted at the N.N. Petrov NMRC of Oncology revealed that special types of BC (excluding lobular carcinomas) accounted for 8.12% of all cases. The most frequent subtypes were mucinous and papillary carcinomas, which generally have a favorable prognosis. In contrast, more aggressive forms—such as metaplastic, neuroendocrine, and micropapillary carcinomas—were associated with worse outcomes and comprised about one-third of all special types.

The findings from the N.N. Petrov NMRC of Oncology (St. Petersburg) align with data from Ankara Oncology Training and Research Hospital (University of Health Sciences), confirming the universality of these patterns. Special types with a favorable prognosis but triple-negative phenotype (e.g., adenoid cystic, acinic cell, and secretory carcinomas) require further investigation due to their rarity and potential clinical significance.

In conclusion, the clinical behavior of special BC types does not always correlate with their biological features, complicating prognosis. Treatment strategies should be based on a comprehensive assessment of tumor morphology, immunohistochemical and molecular profiles, as well as clinical data. A personalized approach to managing these rare BC variants is crucial for improving patient outcomes.

Immunotherapy Combined with Stereotactic Radiotherapy or Isolated Hepatic Perfusion for Metastatic Uveal Melanoma: Preliminary Study Results

Zakhra Magomedova — 2025-09-11

Introduction. Metastatic uveal melanoma (mUM) has a poor prognosis and limited treatment options. Immune checkpoint inhibitors (ICIs) remain a primary systemic therapy despite their modest efficacy. Combining ICIs with local treatments like stereotactic body radiotherapy (SBRT) or melphalan-based isolated hepatic perfusion (IHP) may synergistically improve outcomes.

Aim. This study evaluates the efficacy and safety of anti-PD-1 monotherapy or anti-PD-1+anti-CTLA-4 combination with SBRT or IHP in mUM patients.

Materials and Methods. This ongoing non-comparative cohort study enrolled treatment-naïve mUM patients aged ≥ 18 years (ECOG 0–1) with ≥1 measurable lesion (RECIST 1.1). Patients received ICIs plus SBRT (for ≤ 3 metastases per organ) or IHP (for liver involvement < 50 %), allowing stable extrahepatic metastases.

Results. From September 2019 to April 2025, 43 patients were enrolled (SBRT group: n=21; IHP group: n=22). SBRT group: Objective response rate (ORR) 42.8 %, 6-month progression-free survival (PFS) 66.7 % (95 % CI 42.5–82.5), median PFS 8.6 months (95 % CI 4.4–13.8), median overall survival (OS) 44.7 months (95 % CI 16.9–NR (Not Reached). IHP group: ORR 45 %, 6-month PFS 72 % (95 % CI 48–86), median PFS 10.1 months (95 % CI 5.0–15.5), median OS not reached. Grade 3–5 adverse events occurred in 14.3 (SBRT) and 45.5 % (IHP).

Conclusion. The combination of ICIs with SBRT or IHP shows promising efficacy and acceptable toxicity in mUM, warranting further investigation.

Special Histological Types of Breast Cancer. Favorable Prognosis

Asel G. Kudaibergenova — 2025-06-30

Breast cancer (BC) is a heterogeneous disease, with different clinical, morphological and biological characteristics. These characteristics affect the clinical course of the disease, prognosis and response to systemic treatment. In the vast majority of cases, clinicians encounter invasive non-specific BC, with only 5–15 % of cases presenting as invasive lobular carcinoma. Special morphological subtypes of BC are identified even less often.

Although there are clear treatment standards for non-specific BC, there are none for most special forms. This is partly due to the discrepancy between their biological characteristics and clinical course. Some special variants of BC with an unfavorable immunohistochemical profile may, however, be characterized by a good prognosis. Additionally, both favorable and aggressive courses are encountered within one morphological variant. The true effectiveness of classical methods of treating BC is difficult to assess due to the lack of randomized clinical trials involving patients with special forms of the disease. Most scientific publications on this topic are limited to small retrospective studies or descriptions of individual clinical cases. Consequently, the treatment algorithm for special forms of BC may sometimes differ radically from the recommended standards of treatment and may not correspond to the biological characteristics of the tumor. This publication reflects an analysis of the literature and our own data on favorable forms of BC. These forms include mucinous carcinoma, tubular carcinoma, cribriform carcinoma, papillary carcinoma, medullary carcinoma, apocrine carcinoma, adenosquamous carcinoma, secretory carcinoma, adenoid cystic carcinoma, and acinar cell carcinoma of the breast. The second part considers those with an unfavorable or an uncertain prognosis.