Bi-specific antibodies (BsAbs) represent a groundbreaking advancement in cancer immunotherapy, offering a novel approach to target and eliminate cancer cells by engaging two distinct antigens simultaneously. This review delves into the mechanistic foundations and clinical applications of BsAbs, highlighting their unique dual-targeting capabilities that bridge immune cells with malignant cells to enhance anti-tumor activity. We discuss the various types and design strategies of BsAbs, including their modular structures and engineering innovations that have propelled their efficacy and specificity. The review also examines preclinical and clinical trial data, showcasing the promising results and success stories in different cancer types. Despite their potential, BsAbs face challenges such as manufacturing complexities, stability issues, and toxicity concerns, which we explore alongside current solutions and regulatory considerations. By integrating the latest advancements and emerging trends, this review provides a comprehensive overview of BsAbs and their transformative role in the future of cancer therapy.

Background. The development of local recurrences and distant metastases make the problem of treating locally advanced rectal cancer one of the main problems in modern oncoproctology. The organ-preserving approach, sphincter-preserving operations, the role of a complete clinical response to therapy and the low compliance of patients with adjuvant treatment remain in the focus of attention of scientists.

Aim. Evaluation of the effectiveness of neoadjuvant sequential induction chemotherapy (CT), chemoradiotherapy (CRT), and CapOx consolidating chemotherapy in patients with locally advanced rectal cancer.

Methods. From December 2019 to June 2024, an open-label, randomized phase III study enrolled patients with locally advanced rectal cancer from 3 centers. The inclusion criteria for patients in the study were: histologically confirmed adenocarcinoma, lower and middle rectal cancer, magnetic resonance imaging on a Tesla 3 machine CRM+/4N0-2M0, age 18–75 years, ECOG performance status 0–1. Patients were divided into 2 groups: in the study group, treatment began with 2 courses of induction CT according to the CapOx regimen (oxaliplatin 130 mg/m² on the 1st day of the course intravenously by drip, capecitabine 2000 mg/m² twice a day at 12-hour intervals for 14 days, 7 days break). Then, a long course of chemoradiotherapy was carried out: 44 Gy to the areas of regional metastasis, 50–54 Gy to the primary tumor against the background of CT with capecitabine 825 mg/m² 2 times a day per os on the days of radiation therapy. One to two weeks after the end of CRT, two more courses of consolidation CT were carried out according to the CapOx scheme. A control examination was performed 10–12 weeks after the end of CRT. In the control group, a prolonged course of CRT was carried out: ROD 2 Gy, SOD 44 Gy to the areas of regional metastasis and SOD 50–54 Gy to the primary tumor against the background of CT with capecitabine 825 mg/m² 2 times a day per os on the days of radiation therapy. The primary endpoint was 3-year disease-free survival, calculated from the start of treatment to the date of progression and/or death from any cause or the date of last follow-up. Situations when a patient did not die and did not have disease progression were considered as censored events. Survival was calculated using the Kaplan–Meier method.

Results. 247 patients were included in the study, 178 (72.1 %) underwent a complete course of treatment, 12 (4.9 %) patients are in the process of treatment or waiting for surgery, 25 (10.1 %) patients were excluded from the study for various reasons: organizational problems, refusal of treatment after randomization, detection of a synchronous tumor or metastases before starting treatment. The remaining 32 (12.9 %) patients did not follow the planned treatment protocol due to progression, death or refusal to continue treatment. The prevalence of acute grade III–V toxicities during preoperative treatment was 6.8 % in the CRT + CT group versus 4.7 % in the CRT group. 19 patients with a complete clinical response refused surgical treatment. 6 (5.8 %) patients in the CRT group and 13 (12.1 %) patients from the group in the CRT + CT group (p = 0.05). The disease free median duration of follow-up in group complete clinical response was 1086 days (36.2 months). Sphincter-sparing operations in the CRT + CT group were performed in 54 (65.8 %) patients versus 41 (53.2 %) in the CRT group (p = 0.05). A subgroup analysis of patients with low rectal cancer showed a significant increase in the frequency of sphincter preservation operations in the main group – 23 (46.9 %) versus 16 (31.4 %) in the control group (p = 0.05). On the basis of the Clavien–Dindo classification, the prevalence of surgical complications was similar between the two groups. The total rate of pCR in the CRT + CT group was 41.2 %, which was significantly higher than that in the CRT group (29.8 %). We demonstrated that patients receiving CRT with neoadjuvant CT were well tolerated, with a compliance rate of 71.2 % than those received adjuvant CT (31.2 %, p = 0.05). In particular, 95 % of the patients in the main group underwent 4 planned courses of neoadjuvant CT. 32.5 % of patients in the chemoradiotherapy group did not start adjuvant CT versus 16 % in the study group. The median duration of follow-up was 36 month. Locoregional recurrence was observed in 5 patients: 3 (2.8 %) in the CRT + CT group (1 patient was operated in a non-specialized clinic, after completion of preoperative treatment within the protocol) and 2 (1.9 %) in the CRT group. There was no significant difference in distant metastases: 20 (19.2 %) patients in CRT group and 21 (19.6 %) patients in the study group. There was no significant difference in dieseas-free survival (75 % in the CRT group versus 77 % in the CRT + CT group). Conclusion. Chemoradiotherapy with preoperative CT followed by surgery was efficacious for locally advanced rectal cancer with a significant increase frequency complete clinical response, sphincter-preserving operations, organpreserving treatment including low rectal cancer and rate patient compliance with CT.

Background. Pancreatic cancer (PC) has long been a disease with limited treatment options, where the foundation of therapy was primarily based on cytostatics. However, with the advent of the first KRAS G12C inhibitors, new prospects have emerged for the treatment of advanced PC, highlighting the importance of studying KRAS mutations, which occur in 80–95 % of cases. In this context, it is relevant to analyze the frequency of various KRAS mutations among the Russian population of patients with PC, which could help personalize further diagnostics and therapy.

Aim. To study the features of KRAS status in patients younger and older than 65 years with pancreatic adenocarcinoma in real clinical practice.

Materials and methods. We retrospectively analyzed the data of 590 patients with pancreatic adenocarcinoma who underwent molecular genetic research and treatment at the N. N. Blokhin from 2022 to 2024. Patients with primary multiple malignancies were excluded from the study. Inclusion criteria were the presence of histological verification of the diagnosis and known KRAS, NRAS, BRCA 1/2, CHEK2, PALB2, ATM status. Patients were divided into two age groups, younger and older than 65 years. The primary endpoint was a comparative assessment of the mutation rate in both groups.

Results. 129 patients were included in the analysis. The detection rate of wild-type KRAS in the general population was 24.8 %. The most common mutations in both age groups were p.G12V and p.G12D, accounting for 79.2 % of all mutations in the KRAS gene. The p.G12C mutation was detected in two patients (2 %). Five clinically significant mutations in the BRCA 1/2 genes were identified; the patient with mBRCA1 had a wild type KRAS gene. The remaining 4 patients with a BRCA2 mutation also had a KRAS mutation.

Conclusion. Given the increasing number of drugs that affect KRAS and the ability to detect other alterations in wtKRAS, integration of KRAS testing into routine practice in the evaluation of patients with pancreatic adenocarcinoma is necessary.

Introduction. Historically, the standard for distal margin in rectal cancer surgery has been the 5 cm «rule». Currently, there is a trend to reduction the distal surgical margin. However, intraoperative specimen measurements and histological examination data differ. The phenomenon of surgical shrinkage plays a significant role, especially in determining the distal resection margin, as intraoperative data may not coincide with measurement after fixation of the specimen. Possible differences may lead to doubts about the oncological adequacy of the performed resection boundaries.

Aim. To examine the shrinkage effect of distal resection margin in colorectal cancer after organ formalin fixation.

Materials and methods. The prospective analysis included data of 20 patients with histologically confirmed rectal cancer and sigmoid cancer (adenocarcinoma G1–3) for whom surgical treatment is recommended. The distance between the lower edge of tumor to the distal resection margin was measured after resection (in vivo) and after 5–12 minutes after the last measurement. Then the determination of this distance was made after formalin fixation (in vitro).

Results. The analysis revealed that the average shrinkage of the distal resection margin from in vivo to ex vivo was 30.5 mm (25,5 %) (p = 0.0001). The average shrinkage between in vivo and in vitro bowel samples was 51.0 mm.

Conclusions. Measurement of the distal resection margin under different conditions influences the estimation of the oncological clearence in interpreting the results of pathological report and determining the results of treatment.

Introduction. Ovarian metastases are characterized by low sensitivity to systemic therapy and are often associated with rapid progression and poor prognosis. Given the sensitivity of metastases from cancers of gastrointestinal tract to systemic therapy, the optimal choice of treatment strategy for ovarian metastases is one of the key problems in modern oncology. The aim of the work was to evaluate the effectiveness of bilateral adnexectomy in combination with chemotherapy in patients with ovarian metastases from cancers of gastrointestinal tract.

Aim. The aim of this study was to evaluate the effectiveness of bilateral adnexectomy in combination with chemotherapy in patients with metastatic ovarian lesions originating from gastrointestinal cancer.

Materials and methods. The study included 58 patients aged 37 to 77 years. The inclusion criteria were as follows: histologically verified gastrointestinal cancer; ECOG performance status grade 0–2. Patients with extensive peritoneal dissemination (P3) and brain metastases were excluded from the study. Patients were divided into 2 groups. Group A received combined treatment (adnexectomy / panhysterectomy in combination with drug therapy). Group Б received medications only. Group A was further divided into two subgroups, where Group A1 underwent change of chemotherapy regimen after surgery and Group A2 had no drug therapy adjustment following surgery.

Results. The median progression-free survival (PFS) in group A (with performed adnexectomy or panhysterectomy) was 12 months, while in group Б (no surgery was performed) the result was 4 months. Similar data were obtained when analyzing overall survival (OS) by groups. The median OS in group A was 19, notably these OS figures significantly exceeded the OS in group Б (7 months). Changing the drug therapy regimen after surgery did not demonstrate an increase in OS and PFS in patients of group A1 compared to group A2. Likewise, no statistical differences were found in OS and PFS when patients from group A underwent panhysterectomy as compared with bilateral adnexectomy. Meanwhile, panhysterectomy correlated with a prolonged postoperative recovery period and late systemic treatment resumption.

Conclusions. Combined treatment (bilateral adnexectomy + chemotherapy) significantly increases OS (19 months in group A and 7 months in group Б) and PFS (12 months and 4 months, respectively) in patients with metastatic ovarian disease compared to palliative chemotherapy. Thus, prerequisites for changing clinical practice in this category of patients have been found. The obtained results should be clarified in a randomized study. It is also worth noting that changing the line of chemotherapy is justified only in case of disease progression defined as an increase in the size of nonovarian metastatic foci. This statement should also be confirmed by the results of larger randomized studies.

Introduction. In foreign literature, a number of authors identify such anatomical structures as tubular salivary glands, which, when exposed to radiation, lead to the development of xerostomia. There are still ongoing discussions regarding this discovery and the importance of tubular salivary glands for practical medicine as a risk organ during radiation therapy.

Aim. To study the morphological characteristics of the tubular glands of the nasopharynx on cadaveric material.

Materials and methods. At the Samara Regional Bureau of Forensic Medicine in the simulation center, material was collected from areas of the posterior surface of the nasopharynx and histological examination of the cadaveric material was carried out. Macroscopic and microscopic examination of the autopsy material was carried out. To perform the study, autopsy fragments were subjected to alcohol wiring and embedded in paraffin blocks. Then, 3–4 transverse sections, 5–7 μm thick, were made from each block, followed by staining with hematoxylin and eosin.

Results. Macroscopic and histological examination of nasopharyngeal autopsy specimens from 3 cadavers (2 fragments from each), selected randomly, showed that all 6 studied fragments correspond in structure to glandular structures and contain myoepithelial cells.

Conclusions. Conducting a morphological study after autopsy confirmed the presence of glandular tissue near the tubal ridge along the posterior wall of the nasopharynx, which refers to the salivary glands.

Introduction. Ovarian cancer is one of the leading causes of death from cancer of the female reproductive system. Despite the use of modern drugs, patient survival remains unsatisfactory. In this regard, it is necessary to expand the scope of surgical interventions in this category of patients, which is impossible without performing surgery on the small or large intestine.

Aim. To analyze the long-term results of cytoreductive surgery in patients with advanced ovarian cancer involving the small or large intestine in the tumor process.

Materials and methods. Our retrospective study included 105 patients with histologically verified ovarian cancer who were treated from 2005 to 2017 at N. N. Blokhin Russian Cancer Research Center, the operation of which was accompanied by resection of one or another part of the intestine.

Results. Complete cytoreductive surgery with bowel resection was performed in 39.5 % of cases in the group of patients after neoadjuvant chemotherapy and in 28.4 % of cases in the group of patients without preoperative treatment. There was a significant difference in the rates of non-optimal cytoreduction in the groups of patients with and without preoperative chemotherapy, which amounted to 23.7 and 43.3 %, respectively. When analyzing the long-term results of treatment without taking into account the timing of the operation, it was shown that in patients with complete, optimal and non-optimal cytoreduction, the median PFS was 24.8; 15.1, 11.4 months, the median overall survival was 63,0; 54.7; 36.2 months respectively. Survival analysis taking into account the volume and timing of the operation showed that the best PFS rates (33.9 months) were obtained when the operation was performed as сomplete cytoreduction and without previous drug treatment. A decrease in overall survival was demonstrated with increasing size of the residual tumor, regardless of the timing of the operation. When the operation was performed with no residual tumor in the primary and interval cytoreduction groups, the median life expectancy was 62.9 and 63.3 months, with a residual tumor size of less than 1 cm – 54.7 and 50.7 months, more than 1 cm – 37.6 and 34.9 months respectively.

Conclusion. Surgical treatment of patients with advanced ovarian cancer, aimed at the maximum possible removal of the tumor, is inextricably linked with resection parts, including primarily operations on the small or large intestine. Reducing the size of the residual tumor to achieve complete or optimal cytoreductive surgery, which required bowel resection, naturally increases overall survival rates, regardless of the timing of the surgical intervention.

Aim. Analysis of the effect of histological characteristics on the prognosis of anorectal melanoma (ARM) and melanoma of the skin.

Materials and methods. The study is based on a retrospective single-center analysis of the results of treatment of two groups of patients: with ARM and cutaneous melanoma. N.N. Blokhin National Medical Research Center of Oncology in the period from 2005 to 2023 regarding ARM, were taken from the archives of the pathology department. In turn, a group of patients with cutaneous melanoma was recruited from the «Melanoma Pro» registry. Patients were matched by age, gender and stage of the disease. Disseminated patients were excluded from both groups. A univariate and multivariate analysis of the influence on relapse-free survival and overall survival (OS) of the main clinical characteristics, as well as selected histological prognostic markers of skin melanoma was carried out: multifocal growth, maximum tumor size, maximum Breslow thickness, presence or absence of ulceration, neurotropism and lymphovascular invasion, and depth of invasion (layer).

Results. The study included 21 patients in each group with ARM and skin melanoma. The skin melanoma group included: stage I–II – 9 (42.9 %); stage III – 12 (57.1 %). Data on lymphovascular invasion were available in 68 patients (of which 15 (22.1 %) showed it, p = 0.03), on ulceration – in 428 patients (of which 207 (48.4 %) had it, p = 0.00001), on neurotropism – in 57 patients (of which 3 (5.3 %) showed it, p = 0.35). In the ARM group, there was a tendency for the influence of Breslow invasion of more than 20 mm (hazard ratio 1.028, 95 % confidence interval 0.998–1.060, p = 0.070) and the level of tumor invasion (layer) (hazard ratio 2.117, 95 % confidence interval 0.990–4.525, p = 0.053) on OS in the univariate analysis; in the multivariate analysis, none of the results showed a significant result for OS. In the melanoma group, the prevalence of OS and relapse-free survival among women did not influence our choice. In the skin melanoma group, none of the factors had a significant effect on OS and relapse-free survival in our sample.

Conclusion. Despite the fact that the analysis of the effectiveness of using histological characteristics of skin melanoma showed their potential use as factors of adverse effect on relapse-free survival and OS in ARM, no reliable effect on prognosis was found in the skin melanoma group. Additional studies are needed.

Introduction. Stereotactic radiation therapy (SRT) is increasingly used for the treatment of bone metastases. In cases where stereotactic radiation therapy is contraindicated, an increase in the radiation dose at the site of the lesion can be achieved using the simultaneous integrated boost (SIB).

Aim. The aim of our study is to investigate the role of radiation therapy using the SIB in the treatment of patients with painful spinal metastases.

Materials and methods. The study examined the results of radiation therapy in patients with painful spinal metastases who were treated at the National Medical Research Center of Oncology named after N. N . Blokhin in the period from 2022 to 2023. Patients received radiation therapy with a regimen of 25 Gy in 5 fractions, with dose escalation at the site of the lesion to 30–35 Gy using the simultaneous integrated boost (SIB) (n = 65), or with a regimen of 25 Gy in 5 fractions without the use of SIB (n = 70). Primary endpoint was pain response at 12 months after radiotherapy. Secondary outcomes were long-term treatment results, data from control X-ray examinations, local relapses and mortality.

Results. 12 months after radiation therapy, the survival rate in the main group was 33.8 %, compared to 41.4 % in the control group (p = 0.855). Pain response was achieved in 86.3 % (n = 19) of the main group patients and 75.8 % (n = 22) of the control group patients (p = 0.483). The frequency of recurrence of pain syndrome was significantly higher in the control group (p = 0.031). Neurological status improvement following radiation therapy was observed in 59 % of the main group and 46 % of the control group patients who had neurological deficits related to vertebral metastases. Early complications of radiotherapy of grades I–II were observed in 26 (40 %) of the main group patients and 23 (32.8 %) of the control group. Grade III toxicity was recorded in only 1 (1.42 %) patient in the control group, in the form of increased pain to 7 points on the visual analog scale. No grade IV–V complications were noted.

Conclusions. In radiotherapy of spinal metastases, increasing the radiation dose in the macroscopic lesion area using SIB reduces the risk of pain relapse in the irradiated area. Furthermore, this approach does not increase the risk of radiation complications and may serve as a possible alternative to stereotactic radiation therapy for a specific group of patients.

Background. Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal neoplasms of the gastrointestinal tract, although they account for only 1–2 % of all malignant tumors in the gastrointestinal tract. GISTs most commonly occur in individuals aged 40 to 80 and are primarily located in the stomach. Despite their low metastatic rate, GISTs can invade adjacent tissues, leading to significant clinical symptoms. Diagnosing these tumors is challenging and relies on microscopic and immunohistochemical examinations. This paper presents a clinical case of a patient with a giant gastric GIST, highlighting the importance of timely and accurate diagnosis for radical surgical intervention.

Clinical case. A 59‑year-old female patient, referred to as Patient N., presented to the medical center with a retroperitoneal mass that was discovered during an evaluation after an episode of detected tachycardia. Ultrasonography and further diagnostic imaging revealed a large, heterogeneous mass closely adhering to the gastric wall. Initial biopsies did not yield sufficient material for analysis, prompting a diagnostic laparoscopy, which confirmed the presence of a multinodular tumor consistent with a gastrointestinal stromal tumor (GIST) with high malignant potential. The patient was initiated on targeted therapy with Imatinib, but showed no signs of improvement. Consequently, an atypical gastrectomy and distal pancreatosplenectomy were performed. Post-operative confirmation of the GIST diagnosis was obtained. The patient continues with Imatinib targeted therapy to this day, with no signs of recurrence or disease progression observed.

Conclusion. This case highlights the complexity of treating patients with GISTs, particularly in the context of the tumor’s genetic characteristics. Successful surgical intervention in the treatment of gastric GISTs is crucial when targeted therapy proves ineffective. The results emphasize the importance of a personalized approach to treating such tumors, including mandatory molecular testing (c-KIT, PDGFRA). Although adjuvant treatment with imatinib is effective for patients with mutations in the KIT and PDGFRA genes, its benefits are lacking in patients without such mutations or with mutations causing resistance to therapy. This underscores the significance of an individualized approach in selecting a treatment strategy.