Blokhin National Medical Research Center Research Articles

Assessment of the economic benefit of smoking cessation in cancer patients

Introduction. In 2021, the results of the first large-scale prospective cohort study were published showing the negative impact of post-diagnosis smoking on the prognosis of non-small cell lung cancer (I-IIIа). The purpose of the study is to assess the possible benefits of postdiagnosis smoking cessation of patients with non-small cell lung cancer (NSLC) stage I–IIIa to both the health care system society as a whole. Materials and methods. A mathematical model (calculator) has been developed to calculate the economic benefits of smoking cessation among patients with a confirmed diagnosis of NSCLC (I–IIIa). The calculator uses indicators characterizing the postdiagnosis smoking status of patients with stage I–IIIa NSCLC, the probability of disease progression and survival in the groups of those who continue to smoke and those who quit smoking. These data were obtained from the prospective epidemiologic study performed in the department of clinical epidemiology, N. N. Blokhin NMRC of oncology in cooperation with the IARC. The calculator takes into account the average cost of treating patients with late-stage NSCLC (IIIb-IV stage) in 2020–2022, which is calculated based on an analysis of the medical records of patients who were treated in the Department of Medical Cancer Therapy No. 3 of the of the Federal State Budgetary Institution «N. N. Blokhin National Medical Research Center of Oncology» (Head K. K. Laktionov), statistical data on incidence and mortality from NSCLC in Russia, the Gross Domestic Product (GDP) per capita indicator, and the MINEC Forecast of socio-economic development of the Russian Federation for 2023, 2024 and 2025. Results. Stopping smoking after diagnosis of NSCLC stage I–IIIa results in cost savings due to a reduced likelihood of relapses and an increased number of patients who avoid relapses when quitting smoking. Taking into account the fact that the average cost of treatment for patients with stage IIIb–IV NSCLC is 4,000,000 rubles, savings on treatment due to a decrease in the likelihood of relapses and as a result of an increase in the number of relapse-free patients who quit smoking amounted to 3,321 million rubles. and 9,251 million rubles, respectively, per year. Thus, the total cost savings on treatment will amount to 12,588 million rubles or slightly more than 2.3 million rubles per patient who quit smoking. The second source of saving is maintaining the economically active potential of some patients diagnosed with stage I–IIIa NSCLC, due to increased progression free survival as a result of smoking cessation аmounts to 3 304 million rubles per year in terms of per capita GDP. If 100 % of patients with stage I–IIIa NLCLC hypothetically quit smoking, the potential budget savings could reach a significantly greater value of 29,480 million rubles per year. The economic benefit to society in the total metric of per capita GDP, obtained as a result of increased survival and possible preservation of labor activity, could exceed 14 billion rubles over a 5-year period. Conclusion. Smoking cessation in cancer patients is accompanied not only by clinical benefits, i. e. it reduces mortality and improves survival rates, but also by economic benefits for the healthcare system and the country as a whole.

Factors affecting the effectiveness of conservative treatment of locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinuses

Background. Currently, the main method of treatment of locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinuses is surgical treatment with subsequent radiation/chemoradiation therapy. However, the survival rate of patients has not changed significantly in the last 20 years. Head and neck squamous cell carcinoma is highly sensitive to chemotherapy and radiation which allows to perform treatment even in cases of locally advanced squamous cell carcinomas of the nasal cavity and paranasal sinuses. However, the question of prognostic factors of the effect of chemoradiation therapy remains open. Therefore, determination of these factors is an important problem. Aim. To evaluate the effectiveness of conservative treatment of locally advanced squamous cell carcinoma of the nasal cavity and paranasalsinuses. Materials and methods. The retrospective analysis included 55 patients with squamous cell carcinoma of the nasal cavity and paranasal sinuses (stages III–IVA) who were under observation and receiving treatment at the N.N. Blokhin National Medical Research Center of Oncology between 2000 and 2020. In 50 (90.9 %) patients, treatment began with induction chemotherapy with subsequent radiation therapy per the radical program. In this patient group, treatment effectiveness was evaluated per the RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) criteria. Results. Five-year overall and progression free survival rates were 49.5 and 22.5 %, respectively. Objective response rate after treatment was achieved in 65.5 % of cases: complete response was observed in 38.2 % of cases (n = 21); partial response in 27.3 % (n = 15); stable disease in 18.2 % of cases (n = 10); disease progression in 16.4 % (n = 9). Conclusion. According to the results of the study, conservative treatment is a promising approach in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinuses. Patients with complete response to treatment have the highest odds of cure and improved long-term outcomes.

Diagnostic errors in suspicion for lung tumor

Using clinical cases of patients observed at the Endoscopic Division of the N. N. Blokhin National Medical Research Center of Oncology, we want do demonstrate that while diagnostic radiology has achieved high quality, videoendoscopic examination remains the most objective and usually definitive method in evaluation of contentious situations of differential diagnosis even in cases of seemingly obvious clinical and radiological picture.

The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

The group of hypermethylated long noncoding RNA genes is associated with different types of metastasis in ovarian cancer

Background: Ovarian tumors are characterized by asymptomatic progression until their late stages, when at the time of diagnosis the patient already has extensive metastatic disease. In addition to lymphogenous and hematogenous metastasis in ovarian cancer, there are peritoneal dissemination and metastasis to the greater omentum with ascites; moreover, peritoneal carcinomatosis is the predominant route of metastasizing of ovarian cancer. Epigenetic factors, such as gene methylation, regulatory microRNAs and long non-coding RNAs (lncRNAs), contribute to progression of this cancer. Our previous bioinformatic and experimental studies have identified 13 genes of lncRNAs (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) hypermethylated in the ovarian neoplasms. Aim: To evaluate the clinical significance of methylation levels of 13 lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) associated with various types of ovarian cancer metastasis, including lymphogenous, peritoneal, omental, and distant metastases. Methods: The methylation levels of lncRNA genes GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1 were analyzed by quantitative real-time methylation-specific polymerase chain reaction. We tested 122 duplicate samples of ovarian neoplasms, including 104 malignancies and 18 borderline tumors, as well as 45 peritoneal macro metastases, collected in the N.N. Blokhin National Medical Research Center of Oncology in 2020 to 2023. The study included 21 samples of primary tumor from patients with lymphogenous metastases, 45 samples from patients with peritoneal dissemination, 61 from those with omental metastases, 49 from patients with ascites, and 9 with distant metastases. Results: The tumor samples from the patients with lymphatic nodes metastases showed a significant increase in the methylation level of two lncRNA genes: SNHG6 (p = 0.044) and SNHG12 (p = 0.006). Peritoneal dissemination was associated with hypermethylation of four lncRNA genes: GAS5, HOTAIR, LINC00472 (p 0.05), and most significantly TINCR (p = 0.001). GAS5, HOTAIR, LINC00886 (p 0.05) and most significantly LINC00472 (p 0.001) hypermethylation was typical for omental metastasis, and that of LINC00472 and LINC00886, with ascites (p 0.05). Peritoneal macroscopic metastases demonstrated increased methylation of MAFG-DT (p 0.001) and TP53TG1 (p 0.001) and desmethylation of LINC00886 (p = 0.003) and SNHG12 (p = 0.002), compared to their primary tumors. Conclusion: We performed the analysis of clinical significance of 13 hypermethylated lncRNA genes in ovarian cancer and were the first to show that 10 genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, SNHG6, SNHG12, TINCR, TP53TG1, TUG1) were associated with various types of ovarian tumor metastasis. Also, we were able to determine certain panels of lncRNA, which, if demonstrate abnormal methylation, were specific for lymphogenous and peritoneal metastasis of ovarian tumors.

Methylation of a group of microRNA genes as a marker for the diagnosis and prognosis of non-small cell lung cancer

Objectives. Lung cancer, representing a difficult-to-diagnose heterogeneous malignant neoplasm, is characterized by an asymptomatic course up to late stages, a high incidence of adverse outcomes, and a high probability of metastasis. Its most common form is non-small cell lung cancer (NSCLC). Recent studies have demonstrated a significant role of non-coding RNAs—in particular, microRNAs—in the development of NSCLC. MicroRNAs, which function as post-transcriptional regulators of the expression of protein-coding genes, including those associated with oncogenesis, are involved in the processes of cell proliferation, differentiation, and apoptosis. One of the approaches for regulating the expression of microRNAs themselves is to change the methylation of the CpG island adjacent to the microRNA gene or overlapping it. It has been shown that microRNA genes are several times more likely to undergo methylation than protein-coding genes. The aim of the present work is to study changes in the level of methylation of a number of microRNA genes and compile a potential panel of markers for the diagnosis and prognosis of NSCLC.Methods. Samples of NSCLC tumors were collected and clinically characterized at the Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia. High-molecular-weight DNA was isolated from tissues using a standard method. The level of methylation was analyzed using bisulfite conversion of DNA and quantitative methyl-specific polymerase chain reaction with real-time detection. The significance of differences between the studied groups was assessed by the nonparametric Mann–Whitney U test for independent samples. Differences were considered significant at p < 0.05.Results. The analysis of methylation levels of microRNA genes revealed a significant (p < 0.05) increase in the methylation level of eight microRNA genes: MIR124-1/2/3, MIR125В-1, MIR129-2, MIR137, MIR375, MIR1258, and MIR339 (p < 0.01, false discovery rate ≤ 0.25). On the basis of receiver operating characteristic analysis, a panel of markers is proposed for the diagnosis of NSCLC according to the nature of methylation of the studied microRNA genes in the tumor and in the normal tissue.Conclusions. Our results, which contribute to the understanding of molecular mechanisms involved in NSCLC development, can be used in the development of new diagnostic and prognostic approaches in clinical oncology.

Second line chemotherapy for advanced biliary cancer: FOLFOX versus FOLFIRI: Analysis of retrospective and prospective data

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

Immediate and long-term outcomes of surgical treatment in patients with retroperitoneal and abdominal desmoid fibromatosis: A retrospective study

Background. The main method of treatment of desmoid fibromatosis is surgical, especially in patients with symptomatic disease or in cases of progression during the Look and Stay period. Due to the rarity of the disease, different localization, unpredictability of the clinical course, the lack of generally accepted clear criteria for choosing a treatment method and/or a sequence of treatment methods, the determination of prognostic criteria for the course of the disease is of great scientific and practical interest. Aim. To study the immediate and long-term outcomes of surgical treatment in patients with retroperitoneal and abdominal desmoid fibromatosis. Materials and methods. The study analyzed the data of 121 patients with histologically verified retroperitoneal and abdominal desmoid fibromatosis who underwent surgical treatment at the Blokhin National Medical Research Center of Oncology from 1999 to 2022. Results. In 89% of cases, desmoid tumors are resectable; however, resections of adjacent organs are often required to remove the tumor mass completely. The frequency of combined interventions in the abdominal and retroperitoneal groups was 7.0 and 60.4%, respectively. Tumor cells along the edge of the incision are identified in 15.8% of patients, including 10% of patients with macroscopically detectable residual tumors. Surgical treatment of patients with desmoid tumors is associated with an acceptable complication rate and provides high rates of overall and relapse-free survival. Risk factors for disease-free survival of operated patients are retroperitoneal localization, multicentric tumor growth, and R2 category. Conclusion. The treatment of patients with retroperitoneal and abdominal desmoid tumors should be carried out in specialized clinics with sufficient experience in performing surgical interventions, including combined ones. The treatment approach in patients with desmoid tumors should be selected by a multidisciplinary team based on personalized oncological and functional prognoses in accordance with the prognostic risk groups.

Technologies of modern radiotherapy and development prospects. Quality assurance concept

At the clinic of the N.N. Blokhin National Medical Research Center of Oncology has been using the following conformal irradiation technologies for cancer patients that meet international standards for more than 13 years: 3D conformal radio therapy (3DCRT); intensity modulated radiotherapy (IMRT); volume modulated arc therapy (VMAT); stereotactic radiation technique (SRT); radiotherapy technique with breathing control, total therapeutic irradiation (TRT) technique followed by bone marrow transplantation. The technological complex with which these technologies are implemented has demonstrated an increase in the quality of radiation treatment for cancer patients. However, despite the “advancement” of technology, there are limitations in the ability to reduce dose loads on critical organs for a number of nosologies. Therefore, the prospects for the development of radiotherapy in Russia lie in the creation of several clinical centers for the use of heavy charged particles that have different physical and dosimetric characteristics and, from this point of view, carry other opportunities and prospects. There is great interest in flash therapy.

Quality of Life Questionnaire Validation for Patients with Pelvic Bone Tumors

Quality of life of patients with orthopedic oncological pathology is one of the most important indicators of therapy and rehabilitation effectiveness, a parameter important for establishment of comprehensive approach involving teamwork from doctors and psychologists. Currently, there are many instruments for quality of life evaluation in patients with various chronic diseases including oncological but a specialized questionnaire for patients with pelvic bone tumors does not exist. Nonetheless, characteristics of quality of life of patients with this pathology should be considered for optimal management of psychological and rehabilitation measures, and their dynamics can serve as criteria of treatment and rehabilitation effectiveness.Aim. To develop and test a quality of life questionnaire for patients who underwent surgery on the pelvic bones.Materials and methods. The Quality of Life Questionnaire Pelvic Bone Tumor – 30 (QLQ PBT-30) was developed and tested in 37 patients with tumors of the pelvic bones (20 (54.1 %) males and 17 (45.9 %) females) who were under-going treatment at the General Oncology Division of the N.N. Blokhin National Medical Research Center of Oncology. Mean patient age was 48.15 ± 8.95 years.Results. Psychometric characteristics of the QLQ PBT-30 (validity, reliability) are quite high. Factor analysis confirms correspondence of the factor structure of the questionnaire to the proposed key. Every question contributes to the method structure confirmed by high values of Cronbach’s α.Conclusion. Specialized questionnaire for patients who underwent surgical treatment on pelvic bones can be recommended for use in orthopedic oncology practice for more accurate evaluation of quality of life of patients with tumors of the pelvic bones.

Efficacy and safety of different chemotherapy regimens in patients with disseminated pancreatic cancer over 65 years old

Aim. To evaluate the effectiveness and tolerability of systemic chemotherapy in elderly patients with metastatic pancreatic cancer (mPC) in real clinical practice.Materials and methods. The study included patients with mPC over 65 years of age who received first-line chemotherapy at the N. N. Blokhin National Medical Research Center of Oncology for the period from 2004 to 2023. Any previous antitumor chemotherapy for mPC was an exclusion criterion. The primary endpoint was 1-year overall survival (OS), and the secondary endpoints were ORR, median progression-free survival, median OS, chemotherapy tolerability.Results. The study included 148 patients aged 65 to 86 years with mPC who received first-line chemotherapy. Median progression-free survival among the entire population was 5.2 months. One-year OS among all patients was 32 %. The 1-year OS in mFOLFIRINOX group was 43.4 % and in gemcitabine group – 19.6 %. In a subgroup analysis, median OS with combination treatment was higher than in the gemcitabine monotherapy group (median OS 8.4 months vs. 6.8 months, p = 0.009). Patients with ECOG 2–3 also benefited from combination chemotherapy. Median OS was 8.9 months versus 3.9 months in gemcitabine (p = 0.008). The frequency of an objective response with triple chemotherapy was 66.1 %. In 30.8 % of cases, grade 3–4 neutropenia developed with mFOLFIRINOX, but febrile neutropenia developed only in three patients (5.8 %). The incidence of grade 3–4 adverse events was low, and these chemotherapy regimens were well tolerated.Conclusion. Conducting a triple chemotherapy regimen in elderly patients with mPC is an effective treatment option with an acceptable range of toxicity.

First-line therapy for metastatic uveal melanoma: Experience from a single reference center.

e21514 Background: Metastatic uveal melanoma (mUM) continues to have a poor prognosis with distinct biology from cutaneous melanoma and limited effective treatment options. The main options include immunotherapy (IT, anti-PD-1+/- anti-CTLA-4, tebentafusp), chemotherapy, targeted therapy and local treatment methods for patients with isolated liver metastasis (isolated hepatic perfusion, transarterial chemoembolization, percutaneous hepatic perfusion, radiofrequency ablation). Methods: We conducted a single-center retrospective observation IRB-approved study of first-line therapy for pts age 18 and older with mUM treated at the N.N. Blokhin National Medical Research Center of Oncology from 2020 to 2023. Our objectives were to evaluate clinical outcomes in real-world settings, as well as treatment patterns, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 125 pts included. The mean age was 54 yrs (range: 20-74), and the median time to metastasis from primary tumor was 2 years (range: 0-21). Liver metastases were diagnosed in 92% of patients, lung metastases in 20%, bone metastases in 17%, and soft tissue metastases in 9%. Conclusions: Our data suggest that the combination of systemic and local liver-directed treatment methods may be associated with a survival benefit and higher treatment response to IT in patients with mUM. [Table: see text]

Specifics of regional recurrences in lateral tissue of the neck after surgical treatment of highly differentiated thyroid cancer

Introduction: Despite the fact that highly differentiated thyroid cancer is included in the group of malignant neoplasms with a favorable prognosis, data on the high frequency and recurrence of relapses are reported. The presence of metastatic lymph nodes in HDTC increases the risk of regional relapse by up to 27 %. According to the literature, the factors that increase the risk of recurrence are: histological type, stage, depth of extrathyroid invasion, the presence of metastatic lymph nodes, age, and the volume of primary surgical intervention. Lateral neck dissection should be performed in patients with morphologically verified metastatic thyroid cancer, but there is still no clear consensus on the volume of dissection. Aim: Assessment of factors affecting the risk of regional recurrence in the lateral neck tissue and the localization of recurrence. Materials and methods: The study included 56 patients with HDTC, in whom metastatic lateral neck nodes were identified and verified. All patients previously underwent unilateral or bilateral neck lymph node dissection in various institutions. During the period of dynamic follow-up, these patients revealed regional recurrences in the lateral tissue of the neck. The patients were observed and treated for recurrence at the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. Results: Age over 55 years is a prognostically significant factor affecting the frequency of regional relapse in the lateral neck tissue (p = 0.002). The presence of metastatic nodes in the lateral tissue of the neck at the initial treatment is a prognostically significant factor that increases the risk of regional recurrence in the lateral tissue of the neck (p = 0.017). According to the results of a single-factor analysis, a statistically significant effect of the stage on the risk of regional relapses in the lateral neck tissue was noted (p = 0.014). In 35.7 % of cases, recurrent nodes were localized in the level V. Conclusion: Main risk factors for relapse are clinico-morphological, such as age, aggressive type of HDTC, stage of the disease, N1b status after primary surgery, as well as technical defects during primary surgical treatment.

Efficacy of total neoadjuvant chemotherapy in the FLOT regimen in patients with locally advanced gastric and gastroesophageal junction: results of a phase II study

Background. The established approach notably improving the therapeutic outcomes for locally advanced gastric cancer and gastroesophageal junction cancer, presently entails the amalgamation of perioperative chemotherapy aligned with the FLOT protocol and surgical intervention. However, this approach harbors limitations, as only half of the patient cohort successfully completes the entire prescribed course of drug therapy. The potential solution to this problem lies in the complete transfer of the chemotherapy volume to the preoperative period and the execution of total neoadjuvant chemotherapy with FLOT regimen.Aim. Aim is to conduct a comparative assessment of the efficacy and safety between total neoadjuvant and perioperative chemotherapy with FLOT regimen for patients with locally advanced gastric cancer and gastroesophageal junction cancer.Materials and methods. In a retrospective study we enrolled patients with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer meeting clinical stage criteria T2–4 and N0–3, without of distant metastases, treated between 2014 and 2020 at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation and Moscow City Oncologic Hospital No. 62 Department of Healthcare of Moscow. Participants in the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while those in the experimental group received 8 courses of total neoadjuvant chemotherapy. Both groups received drug therapy according to the FLOT protocol: 5-fluorouracil 2600 mg/m2 , intravenous drip, over 24 hours, leucovorin 200 mg/m2 , intravenous drip, oxaliplatin 85 mg/m2 , intravenous drip, docetaxel 50 mg/m2 , intravenous drip, on day 1, with a 14-day intercourse interval. The primary endpoint was one-year progression-free survival.Results. In the study included 187 patients. Participants were divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The one-year progression-free survival was higher in the total neoadjuvant chemotherapy group at 79 %, compared to 68 % in the perioperative chemotherapy group (HR 0.54, 95 % confidence interval 0.32–0.9, p = 0.02). Median disease-free survival was 27.2 and 19.5 months in the neoadjuvant and perioperative chemotherapy groups, respectively. The tolerability of the entire planned drug treatment regimen was superior in the total neoadjuvant chemotherapy group, reaching 88.4 %, as opposed to 57.6 % in the perioperative chemotherapy group (p = 0.0001).Conclusion. Among patients with locally advanced gastric cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy according to the FLOT protocol, administered over 8 courses, demonstrated enhanced one-year progression-free survival and improved tolerability of the entire planned treatment regimen.

Metal-(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple-Negative Breast Cancer.

Invited for the cover of this issue are Tatiyana Serebryanskaya, Mikhail Kinzhalov and co-workers at St. Petersburg State University, the Research Institute for Physical Chemical Problems, Belarusian State University, Togliatti State University and Blokhin National Medical Research Center of Oncology. The image depicts the shield of Pallas Athena with the structure of a palladium carbene complex that protects against triple-negative breast cancer. Read the full text of the article at 10.1002/chem.202400101.

Surgical treatment of a massive soft tissue neurofibroma in neurofibromatosis type 1

Introduction. Neurofibromas developing in neurofibromatosis type 1 rarely grow to a large size. However, in cases of massive lesions, selection of optimal treatment tactics can be complicated. Clinicians usually resort to surgical treatment which currently serves as an effective instrument for improving patients’ quality of life and for achieving good cosmetic results.Aim. To describe a successful experience of surgical treatment in a patient with giant neurofibroma type 1 affecting a massive pool of soft tissues.Clinical case. Patient, 22 years, sought medical help at the N.N. Blokhin National Medical Research Center of Oncology with diagnosis of neurofibromatosis type 1 with massive lesions in the tissues of the lower third of the back, gluteal region, thighs. The disease has existed since birth, family medical history is fraught: father died of malignant manifestation of a neurogenic tumor. The younger sister is also diagnosed with neurofibromatosis affecting the brain and manifesting through cafe au lait spots on the body. Due to massive tumors significantly decreasing the patient’s quality of life, cytoreductive surgical treatment was prescribed aimed at maximally radical resection of all available tumors to alleviate the patient’s condition.Conclusion. The presented clinical case demonstrates successful experience of surgical treatment of a patient with giant neurofibroma affecting a massive pool of soft tissues.

Validation of the Russian version of Spine Oncology Study Group Outcomes Questionnaire

Introduction. Surgical intervention is the only or main component of combination treatment of the majority of malignant tumors of the spine. Pronounced pain syndrome and neurological deficit caused by spinal tumors significantly worsen disease progression, decrease patients’ quality of life.Aim. To develop a Russian-language version of a specialized questionnaire to study the quality of life of patients suffering from tumor lesions of the spine Spine Oncology Study Group Outcomes Questionnaire (SOSG-OQ).Materials and methods. In 82 patients with tumors of various parts of the spine who are treated at the N.N. Blokhin National Medical Research Center of Oncology, psychometric evaluation of the SOSG-OQ questionnaire was performed confirming its convergent validity and reliability–consistency (Cronbach’s α = 0.899).Results. Exploratory factor analysis confirmed adequacy of the questionnaire’s structure and its conformity to the basic factor model. Instruments of the validated Russian version of the SOSG-OQ questionnaire (text and data analysis instructions) for its use in clinical practice are presented. Results obtained using the new SOSG-OQ questionnaire show a significant decrease in quality of life of patients with spinal tumors. Additionally, after surgery patients described their health-related quality of life significantly higher than prior to treatment.Conclusion. Validated Russian version of the SOSG-OQ questionnaire can be recommended for application in oncological clinic for more precise and differentiated evaluation of performance status, emotional condition, experience of patients, evaluation of life circumstances associated with the disease to promote more targeted and personalized psychological care.

Адъювантная таргетная терапия и анти-PD-1-иммунотерапия у пациентов с меланомой кожи III стадии с мутацией в гене BRAF. Данные реальной клинической практики

Targeted therapy and anti-PD1 immunotherapy are standard of adjuvant stage III (or equivalent stage III) melanoma treatment. Both treatments significantly improve relapse-free survival compared with placebo and ipilimumab. The impact of adjuvant immunotherapy on overall survival remains unclear. Targeted therapy improved 3-year overall survival, but data didn’t reach statistical significance. There is still a lack of direct comparison in randomized trials between targeted therapy and immunotherapy. Data limited to a few retrospective studies. We conducted a single-center observational retrospective study comparing two adjuvant treatment options in BRAF-mutated high-risk melanoma patients who were treated or consulted at the N.N. Blokhin National Medical Research Center of Oncology.

Application of Hybrid Radionuclide Imaging Technologies and Radionuclide Therapy in Patients with Osteogenic Sarcoma

Purpose: To demonstrate the capabilities of various hybrid methods for studying the skeletal system in diagnosing the primary focus and metastases of osteosarcoma. To acquaint specialists with the prospects of using radionuclide therapy in the treatment of patients with osteosarcoma.Material and methods: The material consisted of the most demonstrative cases from the clinical practice of the N.N. Blokhin National Medical Research Center of Oncology.Results: The given examples showed the need to involve all possible radionuclide modalities for diagnosis and, especially, monitoring of patients with osteosarcoma for earlier detection of relapses and metastases.Conclusions: The wider use of modern hybrid research methods (SPECT/CT and PET/CT) makes it possible to expand the possibilities for earlier detection of osteosarcoma metastases not only in bones, but also in other organs and tissues.

Body mass index as a possible predictor of the development of endocrine immune-mediated adverse events during immune checkpoint inhibitors therapy

BACKGROUND: Overweight and obesity have a significant impact on the course and results of treatment of many diseases, including cancer. One of the modern types of antitumor therapy is immune checkpoint inhibitors. Taking into account the high effectiveness of immune checkpoint inhibitors for various types of tumors, it seems interesting to study the initial anthropometric data of patients and assess the possible influence of nutritional status on the development of endocrine immune-mediated adverse events.AIM: To compare groups of patients with different starting body mass index (BMI) before the first administration of the immune checkpoint inhibitors drug and analyze the risk of developing endocrine immune-mediated adverse events in the future.MATERIALS AND METHODS: The single-center study included 172 patients who were recommended antitumor therapy immune checkpoint inhibitors at the N.N. Blokhin National Medical Research Center of Oncology and Moscow City Oncology Hospital №62 in 2020–2022. Measurement of height and body weight with further calculation of BMI was carried out before the first administration of the drug immune checkpoint inhibitors.Depending on the subsequent occurrence of immune-mediated adverse events, patients were divided into groups: those with developed immune-mediated adverse events (any, cutaneous, thyroid) and those without immune-mediated adverse events (any, cutaneous, thyroid).RESULTS: According to the results of our study, in 38 patients (37.3%) out of 102, for whom data on the presence/absence of any immune-mediated adverse events were obtained, the following were recorded: thyropathies (n=13, 12.7%), skin lesions (n=13, 12.7%), gastrointestinal toxicity (n=7, 6.9%), hepatotoxicity (n=4, 3.9%), hypophysitis (n=2, 2%), nephritis (n=2, 2%), diabetes mellitus (DM) (n=1, 1%), hematological toxicity (n=1, 1%), pneumonitis (n=1, 1%), Guillain-Barré syndrome (n=1, 1%). At the same time, in most patients only one immune-mediated adverse event was encountered (n=31, 81.6%), two immune-mediated adverse events were detected significantly less frequently (n=7, 18.4%).When conducting a comparative analysis of groups of patients with developed immune-mediated adverse events, including dermatological ones, or their absence, a statistical trend in differences in BMI was obtained. Using ROC analysis, a BMI cut-off point was determined equal to 28.16 kg/m² for all immune-mediated adverse events and 25.39 kg/m² for skin immune-mediated adverse events, below which, contrary to the available data, the risk of developing immune-mediated adverse events increased, but the diagnostic sensitivity (DS) and diagnostic specificity (DS) turned out to be low.CONCLUSION: We identified a statistical trend in the risk of developing immune-mediated adverse events (primarily dermatological) with a lower BMI before the start of antitumor immunotherapy immune checkpoint inhibitors. More research is required to find a more reliable relationship.