Introduction: There is a lack of information on the role of neoadjuvant chemotherapy in upper rectal cancer. The aim of our research was to investigate the role of neoadjuvant chemotherapy in upper rectal cancer treatment.

Materials and methods: We conducted a retrospective cohort multicenter study to analyze the medical records of patients with upper rectal cancer from 2007 to 2020 obtained from the archive of Research Institute FSBI «N. N. Blokhin Cancer Research Center» of the Ministry of Health of Russia, A. N. Ryzhikh National Medical Research Centre for Coloproctology, Stavropol regional Clinical oncological Dispensary and Kaliningrad oncological Center. All patients were divided into 2 groups: group 1 included patients who underwent neoadjuvant chemotherapy with CAPOX as the first treatment step, and group 2 included patients who underwent upfront surgery. Primary endpoint was 3‑year disease-free survival (DFS) rate. We also estimated the pathological complete response (pCR) rate, treatment toxicity, postoperative morbidity rate (Clavien – Dindo), degree of tumor regression, local recurrence rate, distant metastases rate, 3‑year overall survival (OS) and the neoadjuvant chemotherapy completion rate.

Results: 118 patients were included in the neoadjuvant chemotherapy group and 103 patients — in the surgery group. Study groups were well balanced and comparable for gender, the ASA status and the tumor differentiation grade. More patients in the neoadjuvant chemotherapy group had clinically positive lymph nodes (p = 0.002). Median follow-up period was 36 months. There were no significant differences in 3‑year OS and DFS. The local recurrence rate was 3.9 % in the surgery group versus 0 % in the neoadjuvant chemotherapy group (p = 0.046). There were no significant differences between study groups in the distant metastases rate (p = 0.293). Sixteen (13.6 %) patients had a pCR after neoadjuvant chemotherapy. The neoadjuvant chemotherapy completion rate was 91.5 %. The hematological toxicity grade 3–4 was observed in 3.3 % (4 patients), the non-hematological toxicity grade 3–4 in 3.3 % (4 patients).

Conclusion: NACT has an acceptable toxicity profile, does not impede oncological treatment results, and can be used in a selected group of patients for early systemic control.

The search for biological markers to assess metastatic involvement of the lymph nodes in gastric cancer is one of the key steps in determining treatment tactics. The role of Ki-67 as a marker of cell proliferation in gastric cancer remains relevant. The aim of our study is to determine the Ki-67 threshold value for predicting the lymph nodes metastases. A retrospective analysis of 154 patients with gastric cancer showed an independent and statistically significant relationship between the depth of tumor invasion T (p = 0.002), the differentiation grade G (p = 0.010), the value of the Ki-67 index (p < 0.0001) and metastatic involvement of the lymph nodes. Using ROC analysis we found that Ki-67 ≥ 45 % correlates with the optimal level of sensitivity (55.9 %), specificity (84.2 %) and accuracy (73.4 %) of the method AUC 0.738 (p >< 0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients>< 0.0001) and metastatic involvement of the lymph nodes. Using ROC analysis we found that Ki-67 ≥ 45 % correlates with the optimal level of sensitivity (55.9 %), specificity (84.2 %) and accuracy (73.4 %) of the method AUC 0.738 (p < < 0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients >0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients with Ki-67 > 45 %, we found that the median OS was 32 months [HR 2.2; 95 % CI 1.2–3,9; p = 0.005], while it was not reached in the group with Ki-67 < 45 %.

A Ki-67 level of ≥ 45 % is the optimal threshold for determining the likelihood of lymph node metastasis in gastric cancer.

A lack of evidence-based data on the chemoradiotherapy (CRT) efficacy in patients with squamous cell carcinoma of the rectum (SCCR) makes further study of this topic extremely important.

Aim: The aim of our research was to estimate the efficacy of CRT in patients with SCCR compared to the rectal adenocarcinoma and squamous cell carcinoma of the anal canal (SCCAC).

Materials and methods: Our study was based on analysis of medical records of patients with ICD–X code C20 and ICD-O 8070 / 3, 8070 / 3.1, 80703 in a database from 2007 to 2020 obtained from the archive of Research Institute FSBI “N. N. Blokhin Cancer Research Center” of the Ministry of Health of Russia. We included patients with SCCR who received CRT as initial treatment into the experimental group. Groups with rectal adenocarcinoma and SCCAC were created using propensity-score matching 1:2 taking into account sex, age, the cN clinical stage, histological grade and tumor size. The main study endpoints were 3‑year overall survival (OS) and disease-free survival (DFS) rates, complete clinical response rate and complete clinical or pathological response rate at 6 months after CRT, local recurrence and distant metastases rates, surgery rate.

Results: We included 15 patients in SCCR group and 30 patients in rectal adenocarcinoma group and SCCAC group each. There were no significant differences in parameters that could affect the prognosis. The complete clinical response was achieved in 7 (46.7 %) patients with SCCR versus 3 (10.0 %) patients with adenocarcinoma (p = 0.005) and 24 (80.0 %) patients with SCCAC (p = 0.005). The surgery rate was 26.6 % (4 patients) in SCCR group, 6.67 % (2 patients) in SCCAC group, 90 % (27 patients) in adenocarcinoma group (p < 0.001). The recurrence rate was 26.7 % (4 patients) in SCCR group versus 10.0 % (3 patients) in adenocarcinoma group (p = 0.146) and 6.7 % (2 patients) in SCCAC group (p = 0.063). The metastases rate was 26.7 % (4 patients) in SCCR group, 26.7 % (8 patients) in adenocarcinoma group (p > 0.99). In SCCAC group metastases were detected in 1 (3.3 %) patient, which was significantly different compared to the SCCR group (p = 0.019). Median follow up was 44 months. The 3‑year OS was 78.8 % in SCCR group versus 91.0 % in adenocarcinoma group (p = 0.675), and 86.3 % in SCCAC group (p = 0.953). The 3‑year OS in adenocarcinoma and SCCAC groups did not differ (p = 0.996). The 3‑year DFS was 34.7 % in SCCR group versus 55.6 % in adenocarcinoma group (p = 0.504) and 82.9 % in SCCAC group (p = 0.031). The 3‑year DFS differences in adenocarcinoma and SCCAC groups were significant (p = 0.041).

Conclusions: We have obtained important data on the CRT comparative efficacy in patients with SCCR, SCCAC and rectal adenocarcinoma. The high complete clinical response rate in SCCR group makes it possible to consider the use of CRT as the main treatment method. Results of our research can be used to plan the treatment of patients with SCCR.

Relevance: The need of prophylactic cervical lymph node dissection for the detection of low grade thyroid cancer remains debatable since preoperative examination does not always allow determining the involvement of a group VI regional lymph collector.

Objective: to evaluate the frequency of group VI nodes involvement with clinical N0–Nx based on the results of a morphological examination after performing a preventive central neck lymph node dissection.

Materials and methods: the study included 295 patients who underwent surgery from 2016 to 2022 for papillary thyroid cancer with cT1–T2, N0–Nx. There were 11.5 % of men included (n = 34) and 88.5 % of women (n = 261). Of these, 40.7 % (n = 120) were less than 55 years old. All patients underwent surgical treatment which included thyroidectomy or hemithyroidectomy with cervical lymph node dissection.

Results: The study included 295 patients with cT1 — 247 (83.7 %) and cT2 — 48 (16.3 %). Pathomorphological examination changed the T index in some patients: pT1 was found in 80.3 % of cases (n = 237); рТ2 — in 9.2 % (n = 27); рТ3 — in 10.5 % (n = 31). Central neck lymph nodes involvement was detected in 77 (26.1 %) out of 295 patients. There was a correlation between the frequency of metastases detection and the size of the primary tumor: 22.8 % (n = 54) of metastases with pT1, 33.3 % (n = 9) with pT2, and 45.2 % (n = 14) with pT3. Transient hypocalcemia was found in 32 % of patients with pT1, 69 % with pT2, and 84 % with pT3. Two patients had unilateral transient paresis of the larynx.

Conclusions: Our analysis demonstrates that the preventive central neck lymph node dissection in patients with low grade thyroid cancer is an important component of surgical treatment, which allows to improve the treatment results with a possible subsequent reduction in the risk of distant progression. In this study 77 (26.1 %) of 295 patients had metastases in the lymph nodes of the central neck. The number of postoperative complications affecting the quality of life of patients was acceptable with 0.67 % of paresis of the larynx and 39 % of mild hypocalcemia.

Introduction: The issues of the radiotherapy target volumes in cases of cervical lymph nodes metastases of squamous cell carcinoma of unknown primary (SCCUP) remain unresolved due to the lack of clinical studies. Escalation or de-escalation of treatment may be directly related to prognostic factors. Purpose of this study was to evaluate the results of treatment using ipsilateral (only involved side of the neck) or total (bilaterally neck and pharyngeal mucosa) radiation therapy (RT) and to analyze the influence of clinical factors on overall survival (OS) and progression-free survival (PFS).

Methods: A retrospective non-randomized clinical trial was conducted. Two-year OS and PFS were assessed in 26 SCCUP patients, who underwent combined treatment, including radiation therapy. Inoperable patients received either definitive RT (3.85 %) or sequential chemoradiation therapy (CRT, 11.5 %), or concurrent CRT (3.85 %). Operable patients underwent neoadjuvant RT with lymph node dissection (34.6 %) or lymph node dissection with adjuvant RT (11.5 %) or adjuvant sequential CRT (7.7 %) or adjuvant concurrent CRT (27 %); 50 % of patients received RT in a dose of more than 60 Gy, in 50 % it was less than 60 Gy. In 54 % of patients, only the ipsilateral cervical lymph nodes were included in the irradiation volume while 46 % of patients received RT to the pharyngeal mucosa and lymph nodes of the neck bilaterally (total radiation therapy group).

Results: The median follow-up was 17 months. The 2‑year OS was 71.5 % (95 % CI 49.3–85.3 %), the 2‑year PFS was 72.1 % (95 % CI 44.5–87.6 %). There were no significant differences in 2‑year OS between the ipsilateral and total radiotherapy groups (HR = 1.08 [0.29–4.06], p = 0.904). Only a factor of extranodal extension (ENE) had a statistically significant impact on OS (HR = 6.05 [1.45–25.19], p = 0.0134).

Conclusion: There was no statistically significant difference in 2‑year OS and PFS between the ipsilateral and total radiation therapy groups. A negative prognostic factor is the extranodal extension (ENE) of a metastatic tumor. Prospective randomized trials are needed.

Introduction: Pembrolizumab is a humanized monoclonal antibody selectively blocking the interaction between the PD-1 receptor and its ligands. The drug RPH-075 is a biosimilar to the original Keytruda®.

Objective: To establish the equivalence of pharmacokinetic (PK) properties, as well as pharmacodynamic (PD) parameters, safety, and immunogenicity of the drug RPH-075 compared to Keytruda® in patients with malignant tumors.

Materials and Methods: This multicenter double-blind randomized study included 90 patients with melanoma and non-small cell lung cancer who were randomized into two treatment groups (RPH-075 and Keytruda ®) in 1:1 ratio. In both groups, pembrolizumab was administered as monotherapy at a dose of 200 mg intravenously every 3 weeks until progression or intolerable toxicity. The primary aim of the study was to assess PK after the first administration. The primary endpoint for PK assessment was AUC(0–504), and for safety, it was the frequency of adverse events (AE). The decision on PK equivalence was planned to be made if the two-sided 90 % confidence interval (CI) for the geometric mean ratio of AUC(0–504) after a single administration of each drug would be within 80.00–125.00 %. Secondary endpoints included Cmax after the first administration, as well as the other PK, safety, and immunogenicity parameters. This study also assessed PK and PD parameters after multiple administrations, and a pilot efficacy assessment was planned.

Results: This article presents the analysis of data from the first stage of the study (after the first drug administration with a 3‑week observation period). The data analysis was blinded, and the treatment groups were coded as A and B. The 90 % CI for the geometric mean ratio of AUC(0–504) after the administration of drug A to AUC(0–504) of drug B was 93.50–121.16 %, and for the ratio of B to A, it was 82.54–106.95 %. The obtained intervals met the specified equivalence limit of 80.00–125.00 %, allowing us to conclude that RPH-075 and original Keytruda® are PK equivalent. Both drugs demonstrated comparably high saturation of PD-1 receptors on CD4+ / CD8+ lymphocytes at the end of the first cycle (day 22). Binding antibodies to pembrolizumab were detected in 2 patients (one in each group) over the analyzed period, indicating comparably low immunogenicity for both drugs. Safety profile analysis during this period revealed 7 AEs in 4 patients in group A and 4 AEs in 3 patients in group B. The frequency of AEs did not significantly differ between the groups.

Conclusions: PK, PD, immunogenicity, and safety parameters of the pembrolizumab biosimilar RPH-075 were equivalent to those of the original Keytruda®.

This review evaluates the role of the tumor microenvironment of breast cancer focusing on the evidence showing that tumor-associated macrophages, neutrophils, and mast cells directly participate in tumor initiation, proliferation, and metastasizing. This study also describes microenvironment cells pathologic assessment relevant for prognostication and treatment decision. Tumor-associated macrophages stimulate breast tumor progression, including tumor cell growth, invasion and metastasizing. Tumor-associated neutrophils are more prevalent in patients with severe disease or resistance to treatment and it can be explained by their pro-tumor / immunosuppressive characteristics. The contribution of mast cells to tumor development and progression appears to be a controversial area of research. The ability of mast cells to promote angiogenesis is viewed as a key process in promoting tumor development. However, elevated level of mast cells at tumor sites seems to be connected with improved outcomes.

Chemotherapy-related peripheral neuropathy (CIPN) is a complication which occurs in the most cancer patients receiving taxanes and platinum-based systemic therapy. CIPN includes the wide range of clinical symptoms, and the peripheral sensitive disorders are the most common. Some patients have CIPN-related symptoms persistent after chemotherapy completion. Impact on patient's quality of life and high prevalence among cancer patients make an active search for new ways of CIPN medical correction relevant. We reviewed the existing data on medical prophylaxis and treatment of CIPN and also presented our observation data with CIPN patients. Based on our research results, we showed that the impact of CIPN on a patient's quality's life was spread beyond the peripheral sensitivity disorder. This should be taken into account for further studying of the possible correction of CIPN.

To date, the issue of not only timely diagnosis and treatment of patients with uveal melanoma (UM), but also the prediction of this pathology remains relevant. The technology of fine needle aspiration biopsy (FNAB) makes it possible to assess the risk of developing metastatic disease using tumor specimen in patients undergoing organ-preserving treatment by cytological and molecular genetic testing in the primary intraocular lesion. Here we present a case of newly identified locally advanced (T3a) UM, outline the possibilities of organ-preserving treatment using Gamma Knife stereotactic radiosurgery, and also demonstrate the feasibility of conducting a comprehensive prognostic testing on FNAB material, including cytological and molecular genetic and morphological prognostic factors. The results of this testing have made it possible to recommend a more frequent surveillance monitoring regime for metastatic disease, which ultimately led to the early detection of UM liver metastases, followed by their successful treatment.

A tumor-agnostic approach to cancer treatment that implies the selection of agents targeting specific genetic aberrations and signaling pathways regardless of the tumor site of origin represents a new direction in personalized oncology. Pembrolizumab is the first therapy approved for unresectable microsatellite instability-high (MSI-H) tumors of any location. In 2022, the combination of dabrafenib and trametinib was approved by the US Food and Drug Administration (FDA) for the treatment of patients with solid tumors harboring BRAF V600E mutations. Melanomas, colorectal cancers, and non-small cell lung cancers are BRAF-mutated in 60 %, 15 %, and 5–8 % of cases, respectively. BRAF-mutated glioblastoma (3 %), cholangiocarcinoma (5–7 %), pancreatic cancer (1–16 %), and Langerhans cell histiocytosis (57 %) have also been reported.

We present two case reports of BRAF-mutated salivary gland and pancreatic cancers in patients with progressive disease despite standard-of-care therapy who were treated with a combination of dabrafenib and trametinib according to the agnostic approach.

The presented case reports have demonstrated that the agnostic approach and treatment with BRAF / MEK inhibitors stabilize the disease in patients with BRAF-positive cancers, including those with multiple metastases, and represent an additional therapeutic option for patients with rare BRAF-mutated cancers for which very few pharmacologic options are available.