Voprosy onkologii

Introductory Remarks, Doctor of Medical Sciences, Professor Novikov S.N.

Sergey N. Novikov — 2025-11-05

Safety Assessment of Dose-Escalated 225Ac-PSMA-617 Radioligand Therapy in Patients with Advanced Metastatic Castration-Resistant Prostate Cancer Following Standard Treatment Failure

Tatiana Yu Kochetova — 2025-11-05

Introduction. 225Ac-PSMA is actively used in Russia and worldwide; however, systematic safety data remain limited. Most published studies are retrospective or consist of individual case reports.

Aim. To evaluate the safety and determine the maximum tolerated injected activity of the radiopharmaceutical 225Ac-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC).

Materials and Methods. We conducted a phase I, single-center, open-label, non-randomized clinical trial using a 3 + 3 dose-escalation design. Three patients per cohort with mCRPC progressing after standard therapies received a single intravenous administration of 225Ac-PSMA-617 at activities of 6.0 ± 10 % MBq, 9.0 ± 10 % MBq, and 12.0 ± 10 % MBq, respectively. Following safety evaluation, three additional patients were enrolled at the 12 MBq dose level. Dose-limiting toxicity (DLT) was assessed during a 6-week observation period.

Results. A total of 140 adverse events (AEs) were recorded in all 12 patients (100 %), including 133 mild and 6 moderate AEs. One serious AE (SAE) was unrelated to treatment and did not constitute a DLT. No severe or life-threatening treatment-related AEs were observed. The most frequent drug-related AEs were lymphopenia (75 %), xerostomia (83.3 %), and leukopenia (66.7 %). Absorbed radiation doses to critical organs remained within commonly applied in radiotherapy dose constraints.

Conclusion. 225Ac-PSMA-617 demonstrated a favorable safety profile at doses of 6–12 MBq in patients with mCRPC. The maximum tolerated dose was not reached in any cohort, establishing 12 MBq as the recommended dose for phase II efficacy evaluation. Trial Registration: Registered in the Clinical Trials Permission Registry (No. 530, November 7, 2024).

Preliminary Efficacy and Safety of a Non-Surgical Watch-and-Wait Strategy in Rectal Cancer: A Prospective Single-Center Observational Study

Alexei Mikhailovich Karachun — 2025-11-05

Introduction. The non-surgical Watch-and-Wait strategy has demonstrated favorable outcomes in clinical trials for rectal cancer patients achieving a complete clinical response to neoadjuvant therapy, supporting its adoption in specialized institutions. However, its safety and efficacy in routine clinical practice remain uncertain, particularly regarding patient adherence to surveillance protocols.

Materials and Methods. From 2022 to 2025, we enrolled 65 patients with locally advanced rectal cancer demonstrating complete tumor regression after neoadjuvant therapy in a prospective single-center study at a federal institution. Ongoing surveillance will determine 3-year relapse-free and overall survival rates.

Results. At time of publication, 46 patients (70.8 %) maintained full surveillance compliance. Tumor regrowth occurred in 17 cases (26.2 %), with 15 patients undergoing surgical intervention at our institution, one seeking external surgery, and one refusing operation. Among surgical cases, 13 (86.7 %) achieved R0 resection while 2 were R1.

Conclusion. Final efficacy and safety conclusions will be established upon completion of the 3-year surveillance period.

High-Dose-Rate Endorectal Brachytherapy Boost for Low-Lying Rectal Cancer: Predictors of Complete Clinical Response

Sergey N. Novikov — 2025-11-05

Aim. To evaluate the complete clinical response (cCR) rate following neoadjuvant external beam radiotherapy (EBRT) with endorectal high-dose-rate brachytherapy (ERHDRBT) boost for residual tumor in patients with cT2-3N0-2 low rectal adenocarcinoma.

Materials and Methods. A preliminary analysis included 48 patients with low rectal adenocarcinoma (cT2-3N0-2). Neoadjuvant therapy consisted of EBRT (23-25 fractions of 2 Gy or 5 fractions of 5 Gy) followed by an ERHDRBT boost (3 fractions of 7 Gy) to endoscopically marked residual tumor. Clinical complete response was assessed using standardized criteria: digital rectal examination (absence of palpable mass), endoscopic evaluation (white scar tissue), and magnetic resonance imaging (MRI) findings consistent with complete response.

Results. At 8-12 weeks post-treatment, cCR was achieved in 25/48 patients (52 %). Near-complete response was observed in 6 additional cases. Among 17 surgically managed patients without cCR, pathologic complete response (pCR) was confirmed in 7 cases (41.2 %). The overall complete response rate (cCR + pCR) was 66.6 % (32/48 patients). Response rates varied by stage: cT2N0-1 patients achieved 80 % complete response (16/20), while cT3N0-2 patients showed 60.7 % complete response (17/28). Late grade I-II rectal complications occurred in 29 % of non-operated patients, with no grade III or higher toxicities observed.

Conclusion. ERHDRBT boost to residual tumor following neoadjuvant EBRT yields high complete response rates (60.7-80 %) in low rectal cancer. The substantial pCR rate among surgically managed patients without cCR suggests the need for refined cCR criteria and/or optimized response assessment timing.

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

Alexey V. Novik — 2025-09-11

Carbon radiotherapy of breast tumor with adding high-Z metal nanoparticles using GEANT4 simulation code

Abuzar Shakeri — 2025-11-05

Radiotherapy (RT) is a vital approach in treating tumors, especially as a follow-up to surgical procedures in cancer therapy. In this article, we explored the advancements in treating breast tumors using carbon beams combined with varying concentrations of gold nanoparticles (GNPs). Our simulations, conducted with the GEANT4 code, indicate that as we increase the energy of the carbon beam and its distance from the starting point of the breast phantom, the absorbed dose tends to decrease. This is accompanied by a shift in the location of the Bragg peak (BP) to higher values of x as the incident carbon beam energy rises. Interestingly, we found that the lowest absorbed dose occurs in the absence of GNPs; however, as the injection rate of GNPs increases alongside the carbon beam irradiation, the absorbed dose rises compared to cases without GNP injection. This increase can be attributed to the presence of high-Z nanoparticles, like GNPs, which generate secondary electrons that enhance the dose deposited in both the tumor and its surrounding environment. Our findings suggest that for the studied phantom with the given geometry, a carbon beam energy range of 70 to 110 MeV/u is optimal, with the best results achieved at a Bragg’s energy of 110 MeV/u.

Incidence of Radionecrosis Following Stereotactic Radiosurgery or Stereotactic Radiotherapy for Brain Metastases: A Meta-Analysis

Pavel I. Bliganov — 2025-11-05

Introduction. The incidence of radionecrosis (RN) following stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) using linear accelerators (LINAC) or robotic delivery systems remains incompletely characterized. In contrast to data from gamma knife-based studies, the literature on these radiotherapy (RT) modalities remains limited. This may lead to inaccurate extrapolation of RN rates observed with gamma-based therapies to populations treated with LINAC or robotic techniques, potentially misrepresenting the true incidence of this disease.

Aim. To evaluate the incidence of RN following SRS/SRT delivered via LINAC or robotic systems in patients with brain metastases.

Materials and Methods. This meta-analysis included studies published between 2015 and 2025 identified through PubMed and ScienceDirect. The primary outcome was RN incidence per lesion and per patient. Study selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Statistical analysis was performed using Comprehensive Meta-Analysis software (v3/v4).

Results. Ten publications met inclusion criteria. Pooled analysis demonstrated RN incidence of 7.1 % (95 % CI: 4.1-12.2) per treated lesion and 10.5 % (95 % CI: 6.8-15.8) per patient using random-effects models.

Conclusion. When indirectly compared with gamma knife outcomes, LINAC and robotic SRS/SRT demonstrate comparable RN rates. However, more studies specifically evaluating these modalities in brain metastasis patients are needed to establish more precise estimates.

Combined Treatment of Late Grade III Radiation Proctitis with the Use of Formalin of Reduced Concentration

Inna Vladimirovna Sycheva — 2025-11-05

Introduction. Radiation therapy (RT) is widely employed in the treatment of prostate cancer (PCa). However, a subset of patients experience radiation-induced complications in adjacent organs, including late radiation cystitis, urethritis, and proctitis, which significantly impair quality of life. While 4–10 % formalin coagulation is internationally used for the management of late radiation hemorrhagic proctitis (LRP), this approach carries a risk of severe complications. To mitigate these risks, we reduced the formalin concentration to 2.5 % and evaluated its efficacy in combination with comprehensive conservative therapy.

Aim. To evaluate the efficacy of reduced-concentration (2.5 %) formalin coagulation combined with comprehensive conservative therapy.

Materials and Methods. The study included 76 patients with cT1-3N0M0 prostate cancer who were treated for grade III LRP between 2009 and 2016. Patient age ranged from 53 to 82 years (median: 70 years). All patients had previously undergone combined hormone-radiation therapy at other Russian institutions, including external beam radiotherapy (n = 56), brachytherapy (n = 11), or combined radiotherapy (n = 9). LRP management consisted of comprehensive conservative therapy involving systemic medications and topical applications (microenemas, suppositories, sponges, and tubes) administered in four annual courses over one year. Additionally, 37 patients with inadequate response to conservative therapy underwent single-session chemical coagulation with 2.5% formalin (CCF). Treatment efficacy was evaluated at 6 and 12 months based on changes in radiation injury severity according to RTOG/EORTC criteria and endoscopic findings, comparing patients without CCF (Group I) and those receiving CCF (Group II).

Results. At the 6-month follow-up, therapeutic efficacy was 62 % in Group I and 89 % in Group II (p < 0.01), with complete or near-complete response (grade 0–I) achieved in 15 and 24 % of patients, respectively. By the 12-month assessment, efficacy rates reached 95 and 100 %, respectively, with Group II demonstrating significantly higher rates of complete/near-complete response (97 vs. 59 %). Surgical intervention was required in 2 patients (5%) from Group I and in none from Group II. No complications related to 2.5 % CCF or recurrence of bleeding were observed.

Conclusion. The addition of 2.5 % CCF to comprehensive conservative therapy improves treatment outcomes for grade III LRP without increasing complication rates when patients are appropriately selected.

Moderate hypofractionation of dose in pelvic lymph node irradiation for patients with high and very high risk prostate cancer: preliminary results

Ekaterina Samartseva — 2025-11-05

Introductuion. Hypofractionated radiotherapy for prostate cancer (PCa) has garnered significant interest over the past two decades. To date, only a limited number of randomized studies have evaluated the efficacy and safety of moderately hypofractionated regimens radiotherapy in high-risk and very high-risk PCа. Consequently, the analysis of independent prospective studies investigating the potential of various dose fractionation schedules in the management of this complex patient population is of particular relevance.

Aim. To evaluate the long-term efficacy and safety of moderately hypofractionated radiotherapy with elective pelvic nodal irradiation and a prostate boost, combined with androgen deprivation therapy (ADT), in patients with high and very high-risk prostate adenocarcinoma (HVHR PCa).

Materials and Methods. From 2019 to 2020, 84 patients with HVHR PCa were treated with combined modality therapy, including moderately hypofractionated radiotherapy to the pelvic lymph nodes and prostate concurrent with ADT. External beam radiotherapy was delivered in 13 fractions of 3.0 Gy administered five times per week (EQD₂ α/β = 1.5: 50.1 Gy). A subsequent boost to the prostate and seminal vesicles was delivered using either high-dose-rate brachytherapy (HDR-BT) in a single fraction of 15.0 Gy (64 patients) or stereotactic body radiotherapy (SBRT) in three fractions of 7.0 Gy (20 patients). Radiation-induced toxicity was assessed according to the RTOG/EORTC grading system and the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Results. The 5-year biochemical recurrence-free survival was 83.4 % overall: 88.9 % in high-risk and 80.7 % in very high-risk PCа patients. Local and regional control rates reached 96.4 and 97.6 %, respectively. Early grade II and III genitourinary toxicity rates were 36.9 % and 0 %, while gastrointestinal toxicity rates were 45.2 and 2.4 %, respectively. Late grade II and III toxicities were observed in 8.3 and 2.4 % of patients for genitourinary effects, and 20.2 and 2.4 % for gastrointestinal effects.

Conclusion. Moderately hypofractionated radiotherapy to the pelvic lymph nodes and prostate (13 fractions of 3.0 Gy) followed by a boost to the prostate demonstrates high efficacy with a low risk of severe (grade III or higher) toxicity in patients with HVHR PCa.

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.