Neoadjuvant chemotherapy is a widely used approach in patients with early triple-negative and Her2-positive breast cancer (BC). This allows in vivo evaluation of treatment efficacy and reduction of the local treatment extent in some patients, as well as prognosis assessment and the prescription of adjuvant chemotherapy in patients with residual tumors. The study evaluated the predictive value of estimating tumor response to treatment using the RCB (Residual Cancer Burden) staging system and assessed Ki-67 levels and tumor-infiltrating lymphocyte (TIL) concentrations in residual tumors in patients with primary operable BC with triple-negative phenotype (TN BC) receiving neoadjuvant platinum-based chemotherapy. The study revealed that complex assessment of the RCB, Ki-67, and TILs parameters provides more accurate predictive information compared to simply asserting the presence or absence of a residual tumor, and allows assignment of patients to escalation or de-escalation of adjuvant systemic therapy.

Background. The article presents the results of our study aimed to identify predictors of metastatic regional lymph node involvement based on the biological characteristics of the primary tumor.

Materials and methods. The study involved 200 female patients with histologically verified unicentric invasive breast cancer (BC) T1-4N0-3M0 who were treated in the state healthcare institution Regional Clinical Cancer Center of Ulyanovsk between 2012 and 2015. Clinical, morphological and molecular parameters of the tumor were analyzed.

Results. A unifactorial statistical analysis has shown that the size of the primary tumor node (p = 0.027), histological variant (p < 0.001), malignancy grade (p = 0.027), total malignancy score (TMS, p < 0.001), lymphovascular invasion status (p < 0.001), and HER2-status (p = 0.0002) are predictors of metastatic lymph node involvement. No significant relationship was found between age (p = 0.118), estrogen receptor status (ER, p = 0.092), progesterone receptor status (PR, p = 0.081), Ki-67 index (p = 0.132), molecular subtype of the tumor (p = 0.213) and presence of axillary lymph node metastases.

Conclusion. The primary tumor size, histological variant, malignancy grade, TMS, lymphovascular invasion, and HER2-status are independent risk factors of metastatic involvement of regional lymph nodes and may be used by clinicians for axillary surgery planning in BC patients.

Introduction. The results of randomized MPACT study have demonstrated that the addition of nab-paclitaxel to gemcitabine leads to a statistically significant increase in life expectancy. The main objective of this retrospective study was to obtain up-to-date efficacy and toxicity data for this drug combination in Russian real-world clinical setting.

Materials and methods. The study enrolled patients with morphologically confirmed locally advanced or metastatic pancreatic cancer who had ECOG Performance Status scores of 0-2 and received treatment with gemcitabine and nab-paclitaxel. Immediate and long-term outcomes, as well as treatment toxicity and dose modifications, were assessed.

Results. The study included 142 patients who received treatment from 2009 to 2019 at 17 centers in 11 regions of Russia. Full dose gemcitabine and nab-paclitaxel were administered at baseline in 74 % of the cases. The median number of chemotherapy cycles was 4 (range, from 1 to 16). Nab-paclitaxel dose was reduced in 32 % of the cases, and that of gemcitabine in 23 % of them. Regression analysis revealed no prognostic factors associated with increased toxicity of gemcitabine and nab-paclitaxel administration. However, previous use of two or more chemotherapy lines had an impact on decisions made by physicians, making them reduce the baseline dose of gemcitabine and/or nab-paclitaxel (OR=6.1, 95% CI 1.5-24.2, р=0.010). An objective response was assessed in 134 subjects with positive response observed in 34 cases (25.4 %). The median time to progression was found to be 6.1 months, and the median life expectancy was 14.2 months.

Conclusions. The combination of gemcitabine and nab-paclitaxel exhibits comparatively high efficacy. The acceptable toxicity profile allows its use in selected patients even with ECOG 2 and in the presence of serious comorbidities.

Purpose. To determine the spectrum of febrile neutropenia (FN) complications resulting in critical conditions in patients receiving anti-tumor therapy, and to assess the immediate results of intensive care.

Materials and Methods. This was an observational single-center study with 103 patients, who developed postcytostatic therapy febrile neutropenia progressing to a critical condition. Eligibility criteria included: anti-tumor therapy received within 29 days prior to admission to the Department of Critical and Intensive Care (DCIC) and complicated by FN; critical illness existing on admission or developing within 24 hours of admission to the DCIC; age over 16 years. Recorded data included demographics, vital signs, and test results obtained during the first 24 hours of treatment, which were required to evaluate the severity of adverse events in accordance with the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), the Systemic Inflammatory Response Syndrome (SIRS) criteria and the Sequential Organ Failure Assessment (SOFA) score; 30-day mortality and the subsequent anti-tumor therapy start date.

Results. Out of 5114 admissions of 3608 patients, 114 met the eligibility criteria of the study, and all necessary data were obtained for 103 subjects. Patients with solid tumors accounted for two thirds of the study sample. The mean time from start of chemotherapy to critical condition was found to be 12.64±5.61 days. In 96% of the cases, the reason for hospitalization was a suspected systemic infection leading to organic disorders. Infection was the actual cause of the critical condition only in 48.5% of cases. The inpatient mortality rate was 31%; more than 70% of survivors continued anti-tumor therapy.

Conclusion. The need to determine the cause of organic disorders, which often result from causes other than infection or sepsis as it is currently understood, is among the factors complicating the management of cancer patients whose critical condition is due to drug-induced febrile neutropenia and organ failure. The availability of intensive care ensures high short-term survival and enables further use of appropriate anti-tumor treatment.

Introduction. Treatment of malignant neoplasms often requires adjuvant chemotherapy (ACT). In real-life clinical practice, a high proportion of patients develop serious toxicities of anticancer therapy. Thus, the need to reduce treatment toxicity while maintaining the same dose levels of chemotherapeutic agents is a pressing challenge in oncology. This article presents the results of the study assessing the effects of the complex nutraceutical Oncoxin on ACT tolerability.

Materials and methods. The study included 133 patients aged 50 to 70 years with stage IIB — IIIC gastric cancer or stage IIB — IIIA non-small-cell lung cancer; 84 patients received Oncoxin, and 49 were in the control group.

Results. The study revealed that after two weeks, patients receiving Oncocoxin had a twice higher chance of significant (obvious) improvement in their quality of life (ESAS questionnaire) compared to the control group: OR 2.07 [95% CI 1.00-4.29]. By the end of the follow-up period (3 weeks), patients receiving Oncoxin had a significantly higher albumin level compared to the control group (38.1 [95% CI 37.1-39.1] g/L and 35.5 [95% CI 33.9-37.0], р =0.03, respectively). Moreover, the use of Oncoxin allowed significant reducing ACT-related liver toxicity.

Conclusions. This study conducted within our current clinical practice showed for the first time a high efficacy of Oncoxin in improving the quality of life of patients and reducing ACT toxicity.

Background. Ovarian malignancies constitute the 8th most common cancer in women with regard to morbidity and the 6th most common with regard to mortality. Survival of patients with ovarian cancer depends on the type of surgery and the size of the residual tumour. An «aggressive» surgical approach is currently adopted in the treatment of ovarian malignancies, which is aimed at removing all visible tumour lesions and subsequent regional chemotherapy. However, outcomes of treatment remain unsatisfactory, which indicates a need for a search for new, alternative treatment methods. Intraperitoneal hyperthermic chemoperfusion is one of such methods being introduced into clinical practice.

Purpose. To evaluate the effectiveness of hyperthermic chemoperfusion in complex therapy regimens for patients with advanced ovarian cancer after optimal interval surgery.

Materials and methods. A retrospective, single-centre, non-randomized study was conducted at the State Budgetary Institution of Health Care Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine from January 2014 to February 2019. The study material included data from an observation of 61 patients diagnosed with ovarian cancer stage IIIA-C. Tumours were staged according to the FIGO / TNM classification (2009). Prior to initiation of therapy, all patients underwent an examination that included PET / CT and BRCA mutation testing. At the first stage, all subjects received 3 cycles of neoadjuvant combination chemotherapy (NACCT) according to the following regimen: paclitaxel 175 mg/m² and carboplatin AUC 5-6 every 3 weeks.

At the second stage, all patients had cytoreductive surgery and then were divided into 3 groups. Study enrollment was sequential: Group 1 consisted of 15 subjects (24.6%) who were treated with hyperthermic intraperitoneal chemoperfusion (HIPEC) with paclitaxel 100 mg/m², Group 2 included 20 patients (32.8%) receiving HIPEC with cisplatin 100 mg/m², and Group 3 was composed of 26 control patients (42.6 %) who had no HIPEC. Progression-free survival, i. e., the time from the date of diagnosis to disease progression as established using objective methods, was used as the study endpoint.

Study results. Treatment outcomes after first-line chemotherapy with interval surgery were analyzed. According to the RESIST 1.1 1 criteria, in Group 1 16 patients (45.7 %) had complete response, 12 subjects (34.2 %) had partial response, 4 patients (11.4%) had disease stabilization, while disease progression was observed in 3 cases (8.5%). In Group 2, complete response, partial response, disease stabilization, and progression were observed in 13 (50%), 7 (26.9%), 3 (11.5%), and 3 (11.5%) cases, respectively.

Background. Tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CI) have been established as effective treatment for mRCC, but only a minority of patients achieves complete response and additional strategies are necessary to improve the efficacy of these agents. We have designed a prospective phase 1b «Volga» study to determine the safety and efficacy of extracranial SBRT in patients with clear-cell mRCC.

Methods. Patients were included if they had stable disease for at least 4 months on TKI or CI. SBRT was delivered to an organ with multiple comparable lesions, where one lesion was in the treatment target (target lesion) and the other lesion was intentionally left untreated (control lesion). Dose of radiation and number of fractions were determined based on target lesion localization and the proximity of organs at risk. Response in both target and control lesions was scored using RECIST 1.1 criteria at least 2 months after completion of SBRT. Primary endpoint was the rate of adverse events of SBRT and secondary endpoints included the rate of reduction in target lesion size and time to progression of the first (target) and the second (control) lesions.

Results. 17 patients were enrolled since November 2016 (14 men and 3 women, median age — 54,5 years old, range 32 -72), 6 of them initially were diagnosed with metastatic RCC and the reminders developed distant metastases within 6 months — 5 years since radical nephrectomy. Twelve patients received TKI and 5 received nivolumab. SBRT was delivered to lungs (n=5), bones (n=4), lymph nodes (n=4), liver (n=1), primary RCC (n=1), and locally recurrent RCC (n=2). Equivalent Dose (EQD) with alpha/beta ratio of 2.6 was 114 Gy (range, 40-276 Gy). With a median follow-up of 8 months (range, 3 -18), cumulative rate of SBRT-related toxicity (grade 1) was 12 % (n=2), consisting of esophagitis (n=1) and skin erythema (n=1). No grade 2 or higher toxicity was detected. Radiographic response in the target lesion was seen in 13 patients (76 %), with complete response in 5 (29 %) patients and partial response in 8 (47 %) including abscopal effect in 1 patient. Control lesions remained stable in 16 patients. The difference between response in target and control lesions as judged by mean sizes of these lesions before and at 2 months after SBRT was statistically significant (p<0.01). Fraction size of equal to or greater than 10 Gy was associated with complete response in the target lesion (p<0.01).

Conclusion. Extracranial SBRT in patients with mRCC treated with TKI or CI is well tolerated and could be effective. This approach will be studied in an expanded cohort of patients.

Background. Inhibition of fibroblast growth factor receptor type 2 (FGFR2) appears to be appropriate in patients with tumors expressing or amplifying FGFR2. The toxicity of allosteric FGFR2 inhibitors has not been previously studied.

Purpose. Evaluation of the toxicity of the anticancer drug alofanib (RPT835), allosteric inhibitor of fibroblast growth factor receptor 2 type (FGFR2), in standard experimental in-vivo models in rodents and non-rodents.

Material and methods. The general toxic effect of the alofanib was studied in an acute and chronic experiment on outbred animals (rats and rabbits) of both sexes. An experimental study was conducted in accordance with the ethical principles of handling laboratory animals.

Results. The assumption that inhibition of FGFR2 provides a low level of toxicity has been proved. It was established that alofanib belongs to the 4 class of low-toxic chemical substances according to the classification of hazard levels of toxic effects of drugs and to the low-risk drugs by the value of the index of the therapeutic action, as well as to the 3 class (low-toxic drugs) according to the class of hazards for clinical application. Alofanib doesn»t cause allergenic and immunotoxic effects as well as doesn»t have pyrogenic properties. Increase of phosphates level (class-specific adverse effect of FGFR2 inhibitors) was statistically significant but less evident. During the study was noticed such an adverse effect as inhibition of spermatogenesis.

Conclusion. Alofanib belongs to the classes of low-hazard and low-toxic chemicals and can be studied in a clinical study.

Although gallbladder and biliary tract cancer is a rather rare group of diseases, it is among the pressing issues of modern oncology. Adequate surgery is the only curative method that can give a chance for recovery for a small proportion of patients at early stages of the disease. The scope of opportunities of drug therapy in biliary tract cancer is limited by the low effectiveness of the few currently available cytostatics. The addition of chemotherapy has little effect on the long-term outcome of surgery and other local interventions. Apparently, future treatments for these patients should be developed based on studies of targeted therapy and its combination with standard cytotoxic therapy, as well as possible targeting of anticancer immune response, which necessitates a search for immunotherapy efficacy predictors. The objective of this article is to consider the practical potential of drug therapy for biliary tract cancer and to review the studies that looked into molecular genetic targets and effective combinations of existing drugs, analyzing possible practical applications of the study results.