Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-83-91
V. Yarovaya, А. V. Golanov, V. V. Nazarova, А. R. Zaretskii, I. A. Levashov, А. К. Kulagina, Т. V. Melnikova, А. D. Matyaeva, А. Yarovoy
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.
迄今为止，不仅要及时诊断和治疗葡萄膜黑色素瘤（UM）患者，还要对这种病理变化进行预测，这个问题仍然十分重要。细针穿刺活检（FNAB）技术可通过对眼内原发病灶进行细胞学和分子遗传学检测，评估接受器官保留治疗的患者肿瘤标本发生转移性疾病的风险。在此，我们介绍了一例新发现的局部晚期（T3a）UM，概述了使用伽玛刀立体定向放射外科手术进行保留器官治疗的可能性，同时还展示了对 FNAB 材料进行全面预后检测的可行性，包括细胞学和分子遗传学及形态学预后因素。这项检测的结果使我们有可能建议对转移性疾病进行更频繁的监测，从而最终及早发现 UM 肝转移灶，并对其进行成功治疗。
{"title":"Uveal melanoma: the value of molecular genetic testing for early detection of metastatic disease. Clinical case","authors":"V. Yarovaya, А. V. Golanov, V. V. Nazarova, А. R. Zaretskii, I. A. Levashov, А. К. Kulagina, Т. V. Melnikova, А. D. Matyaeva, А. Yarovoy","doi":"10.18027/2224-5057-2024-14-1-83-91","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-83-91","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140239834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-9-20
S. N. Lukmonov, Y. V. Belenkaya, S. Gordeev, A. J. Sadikov, Z. Mamedli
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.
{"title":"Preliminary results of surgical treatment and neoadjuvant chemotherapy in upper rectal cancer","authors":"S. N. Lukmonov, Y. V. Belenkaya, S. Gordeev, A. J. Sadikov, Z. Mamedli","doi":"10.18027/2224-5057-2024-14-1-9-20","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-9-20","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140238504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-39-46
М. S. Tigrov, L. Yakovleva, М. А. Kropotov, S. S. Menshikova
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.
{"title":"Preventive central neck lymph node dissection as a stage in the treatment of papillary thyroid cancer","authors":"М. S. Tigrov, L. Yakovleva, М. А. Kropotov, S. S. Menshikova","doi":"10.18027/2224-5057-2024-14-1-39-46","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-39-46","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140239361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-67-73
К. S. Titov, D. Grekov, Е. I. Zakurdaev, Z. V. Lorie, О. V. Paklina, Е. N. Gordienko
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.
{"title":"Importance of tumor microenvironment inflammation cells in breast cancer","authors":"К. S. Titov, D. Grekov, Е. I. Zakurdaev, Z. V. Lorie, О. V. Paklina, Е. N. Gordienko","doi":"10.18027/2224-5057-2024-14-1-67-73","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-67-73","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140241326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-21-29
Е. А. Ashimov, D. А. Chichevatov, V. V. Radovsky, Е. А. Kolesnikova, S. А. Klimin, S. V. Gamayunov, V. Е. Zagainov, N. М. Kiselev
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.
{"title":"Determination of the Ki-67 threshold value for predicting lymph nodes involvement in patients with gastric cancer","authors":"Е. А. Ashimov, D. А. Chichevatov, V. V. Radovsky, Е. А. Kolesnikova, S. А. Klimin, S. V. Gamayunov, V. Е. Zagainov, N. М. Kiselev","doi":"10.18027/2224-5057-2024-14-1-21-29","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-21-29","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140237442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-56-66
I. V. Samoylenko, I. A. Pokataev, L. G. Zhukova, D. Stroyakovsky, R. V. Orlova, А. M. Mudunov, М. В. Pak, Е. V. Zernova, А. V. Sobolev, А. S. Mochalova, B. Y. Alekseev, М. I. Sekacheva, Е. V. Ledin, А. V. Petkova, Е. К. Khanonina, А. I. Podolyakina, V. А. Razzhivina
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®.
{"title":"Study of the pharmacokinetics, pharmacodynamics, and safety of the biosimilar pembrolizumab RPH-075 compared to Keytruda® in patients with malignant neoplasms","authors":"I. V. Samoylenko, I. A. Pokataev, L. G. Zhukova, D. Stroyakovsky, R. V. Orlova, А. M. Mudunov, М. В. Pak, Е. V. Zernova, А. V. Sobolev, А. S. Mochalova, B. Y. Alekseev, М. I. Sekacheva, Е. V. Ledin, А. V. Petkova, Е. К. Khanonina, А. I. Podolyakina, V. А. Razzhivina","doi":"10.18027/2224-5057-2024-14-1-56-66","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-56-66","url":null,"abstract":"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®.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140239216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-92-98
N. V. Prokudina, М. М. Kramchaninov
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.
{"title":"Case reports of BRAF V600E-mutated tumors effectively treated using the agnostic approach","authors":"N. V. Prokudina, М. М. Kramchaninov","doi":"10.18027/2224-5057-2024-14-1-92-98","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-92-98","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140240018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-15DOI: 10.18027/2224-5057-2024-14-1-47-55
А. V. Sheiko
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.
导言：由于缺乏临床研究，原发灶不明的鳞状细胞癌（SCCUP）宫颈淋巴结转移病例的放疗靶体积问题仍未解决。治疗升级或降级可能与预后因素直接相关。本研究旨在评估同侧（仅颈部受累侧）或全侧（双侧颈部和咽部粘膜）放疗（RT）的治疗效果，并分析临床因素对总生存期（OS）和无进展生存期（PFS）的影响：方法：进行了一项回顾性非随机临床试验。方法：进行了一项回顾性非随机临床试验，评估了26名SCCUP患者两年的OS和PFS，这些患者接受了包括放疗在内的综合治疗。不能手术的患者接受明确的 RT（3.85%）或序贯化放疗（CRT，11.5%），或同时接受 CRT（3.85%）。可手术患者接受了淋巴结清扫的新辅助 RT（34.6%）或淋巴结清扫辅助 RT（11.5%）或辅助序贯 CRT（7.7%）或辅助同期 CRT（27%）；50% 的患者接受了剂量超过 60 Gy 的 RT，50% 的患者接受了剂量低于 60 Gy 的 RT。54%的患者的照射范围仅包括同侧颈部淋巴结，46%的患者接受了咽部粘膜和双侧颈部淋巴结的RT（全放疗组）：中位随访时间为17个月。结果：中位随访时间为 17 个月，2 年 OS 为 71.5%（95% CI 49.3-85.3%），2 年 PFS 为 72.1%（95% CI 44.5-87.6%）。同侧放疗组和全放疗组的 2 年 OS 无明显差异（HR = 1.08 [0.29-4.06]，P = 0.904）。只有结节外扩展（ENE）因素对OS有统计学意义的影响（HR = 6.05 [1.45-25.19], p = 0.0134）：同侧放疗组和全放疗组的2年OS和PFS差异无统计学意义。转移性肿瘤的结节外扩展（ENE）是一个不利的预后因素。需要进行前瞻性随机试验。
{"title":"Influence of the radiotherapy target volume and prognostic factors on the results of treatment of patients with cervical lymph nodes metastases of squamous cell carcinoma of unknown primary","authors":"А. V. Sheiko","doi":"10.18027/2224-5057-2024-14-1-47-55","DOIUrl":"https://doi.org/10.18027/2224-5057-2024-14-1-47-55","url":null,"abstract":"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.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140241176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-16DOI: 10.18027/2224-5057-2023-13-4-46-59
T. Tikhomirova, A. Tyulyandina, A. A. Rumyantsev, E. Israelyan, T. V. Kekeeva, O. Vedrova, M. L. Filipenko, L. N. Lyubchenko, I. A. Demidova, E. N. Imyanitov, S. Andreev, S. Khokhlova, V. Saevets, G. B. Statsenko, L. A. Kolomiets, S. A. Tkachenko, I. A. Koroleva, A. S. Lisyanskaya, O. Bakashvili, L. Krikunova, E. P. Solovieva, D. Ponomarenko, L. Vladimirova, S. Krasilnikov, V. B. Shirinkin, D. D. Sakaeva, E. A. Rumyantseva, S. A. Emeliyanov, D. Stroyakovskiy, E. G. Novikova, E. A. Ronina, V. I. Vladimirov, O. Y. Novikova, L. Zagumennova, V. V. Gorobtsova, E. V. Cherepanova, E. N. Pashkova, V. Moiseyenko, F. G. Ivanova, D. Udovitsa, V. Karaseva, S. Tyulyandin
Purpose: To evaluate the proportion of BRCA1 / 2 mutations in patients with serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum in Russia, to evaluate the percentage of germinal and somatic mutations, to identify the spectrum of mutations in BRCA1 / 2 genes, to evaluate clinical and morphological features of the BRCA-associated ovarian cancer (OC).Patients and methods: The study enrolled patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. Biological material (blood, tumor tissue) was collected, followed by molecular genetic analysis. The method of mutations detecting in the blood were: allele-specific PCR, high-resolution melting (HRM), Sanger sequencing method. Advanced genetic testing included the use of generation sequencing (NGS) and multiplex amplification of ligated probes (MLPA). The collection of clinical data, family history, clinical and morphological characteristics of the tumor was performed.Results: 500 patients were included in the study, the evaluation of BRCA1 / 2 mutations was performed in 496 patients (99,2 %). The frequency of BRCA1 / 2 mutations in the Russian patient population was 28,4 % (n = 141 / 496). The incidence of germinal mutations was 23,5 % (n = 117 / 141), and somatic — 4,8 % (n = 24 / 141). Frequent mutations in the Russian population were identified in 50 % of cases. When analyzing the ethnicity of patients in the Russian Federation BRCA-associated OC was most common in Russian (83,6 %, n = 118 / 141), Ukrainian (4,2 %, n = 6 / 141) and Tatar (3,5 %, n = 5 / 141) women. A family history of cancer was detected in 44 % of patients (n = 62 / 141) with BRCA1 / 2 mutations.Conclusions: Due to the high frequency of germinal and somatic BRCA1 / 2 mutations in the Russian patients it is recommended to conduct the advanced testing methods not only in blood samples but also in tumor tissue.
{"title":"BRCA-associated ovarian cancer in the russian patient population. Analysis of the non-interventional study Ovatar","authors":"T. Tikhomirova, A. Tyulyandina, A. A. Rumyantsev, E. Israelyan, T. V. Kekeeva, O. Vedrova, M. L. Filipenko, L. N. Lyubchenko, I. A. Demidova, E. N. Imyanitov, S. Andreev, S. Khokhlova, V. Saevets, G. B. Statsenko, L. A. Kolomiets, S. A. Tkachenko, I. A. Koroleva, A. S. Lisyanskaya, O. Bakashvili, L. Krikunova, E. P. Solovieva, D. Ponomarenko, L. Vladimirova, S. Krasilnikov, V. B. Shirinkin, D. D. Sakaeva, E. A. Rumyantseva, S. A. Emeliyanov, D. Stroyakovskiy, E. G. Novikova, E. A. Ronina, V. I. Vladimirov, O. Y. Novikova, L. Zagumennova, V. V. Gorobtsova, E. V. Cherepanova, E. N. Pashkova, V. Moiseyenko, F. G. Ivanova, D. Udovitsa, V. Karaseva, S. Tyulyandin","doi":"10.18027/2224-5057-2023-13-4-46-59","DOIUrl":"https://doi.org/10.18027/2224-5057-2023-13-4-46-59","url":null,"abstract":"Purpose: To evaluate the proportion of BRCA1 / 2 mutations in patients with serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum in Russia, to evaluate the percentage of germinal and somatic mutations, to identify the spectrum of mutations in BRCA1 / 2 genes, to evaluate clinical and morphological features of the BRCA-associated ovarian cancer (OC).Patients and methods: The study enrolled patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. Biological material (blood, tumor tissue) was collected, followed by molecular genetic analysis. The method of mutations detecting in the blood were: allele-specific PCR, high-resolution melting (HRM), Sanger sequencing method. Advanced genetic testing included the use of generation sequencing (NGS) and multiplex amplification of ligated probes (MLPA). The collection of clinical data, family history, clinical and morphological characteristics of the tumor was performed.Results: 500 patients were included in the study, the evaluation of BRCA1 / 2 mutations was performed in 496 patients (99,2 %). The frequency of BRCA1 / 2 mutations in the Russian patient population was 28,4 % (n = 141 / 496). The incidence of germinal mutations was 23,5 % (n = 117 / 141), and somatic — 4,8 % (n = 24 / 141). Frequent mutations in the Russian population were identified in 50 % of cases. When analyzing the ethnicity of patients in the Russian Federation BRCA-associated OC was most common in Russian (83,6 %, n = 118 / 141), Ukrainian (4,2 %, n = 6 / 141) and Tatar (3,5 %, n = 5 / 141) women. A family history of cancer was detected in 44 % of patients (n = 62 / 141) with BRCA1 / 2 mutations.Conclusions: Due to the high frequency of germinal and somatic BRCA1 / 2 mutations in the Russian patients it is recommended to conduct the advanced testing methods not only in blood samples but also in tumor tissue.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139619843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-15DOI: 10.18027/2224-5057-2023-13-4-7-17
A. Kalinin, I. G. Avdyukhin, S. N. Nered, N. S. Besova, A. A. Tryakin, E. V. Artamonova, T. A. Titova, E. Obarevich, E. O. Ignatova, N. A. Kozlov, O. Rossomakhina, N. A. Shishkina, E. Kolobanova, O. Malikhova, M. G. Abgaryan, M. Nikulin, P. Arkhiri, L. A. Vashakmadze, I. Peregorodiev, E. A. Suleimanov, I. Stilidi
Introduction: The main current approach to the treatment of patients with resectable cancer of the stomach and gastroesophageal junction (GEJ) is perioperative FLOT chemotherapy. The mFOLFIRINOX regimen has been shown to be effective and safe in disseminated adenocarcinoma of the stomach and GEJ. This article presents preliminary results of the efficacy and safety assessment of perioperative FOLFIRINOX chemotherapy in patients with resectable cancer of the stomach and gastroesophageal junction.Materials and Methods: The FOLFIRINOX / FLOT study is a phase 2 / 3 open-label, randomized trial. Study enrollment was started in January 2019 and is currently ongoing. The inclusion criteria are: histologically confirmed resectable adenocarcinoma of the stomach or gastroesophageal junction, Siewert types II–III, clinical stage cT4aN0M0, cT1–4N1–3M0 or cT2–4N0–3M0, with total or subtotal involvement of the stomach. The following regimens were used for perioperative chemotherapy: FLOT — docetaxel 50 mg / m2 on day 1, oxaliplatin 85 mg / m2 on day 1, leucovorin 200 mg / 2 on day 1, 5FU 2600 mg / m2 × 24 hours starting on day 1, or mFOLFIRINOX — irinotecan 180 mg / m2 on day 1, oxaliplatin 85 mg / 2 on day 1, leucovorin 200 mg / m2 on day 1, 5FU 250 mg / m2 bolus on day 1 and then 2200 mg / m2 × 48 hours on day 1. The primary endpoint was 5‑year overall survival.Results: All planned preoperative courses of chemotherapy had been administered to 25 (86 %) patients in the FLOT group (n = 29) and 22 (92 %) patients in the FOLFIRINOX group (n = 24). Four (12 %) and 2 (8 %) patients in the FLOT and FOLFIRINOX groups, respectively, discontinued the treatment. The surgical staging was used in 48 patients (91 %) (25 [86 %] in the FLOT group and 23 [96 %] in the FOLFIRINOX group). Complete tumor regression (Mandard grade 1) had been achieved in 4 patients (2 [7 %] in the FLOT group and 2 [8 %] in the FOLFIRINOX group). Postoperative complications were detected in 2 patients (8 %) in the FLOT group and 4 (17 %) in the FOLFRIRNOX group. Thirty-three patients (62 %) received all scheduled postoperative treatment courses (n = 19, 66 % for FLOT and n = 14, 58 % for FOLFIRINOX).Conclusions: The preliminary results of the FOLFIRINOX / FLOT study showed comparable tolerability of the regimens and comparable complete pathological response rates. However, there was a higher incidence of postoperative complications detected among patients who received the FOLFIRINOX regimen compared to the FLOT group.
{"title":"Efficacy of perioperative FOLFIRINOX chemotherapy versus FLOT chemotherapy in patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (SIEWERT types II–III, cT4aN0M0, T1–4cN+ cM0): preliminary results of the study","authors":"A. Kalinin, I. G. Avdyukhin, S. N. Nered, N. S. Besova, A. A. Tryakin, E. V. Artamonova, T. A. Titova, E. Obarevich, E. O. Ignatova, N. A. Kozlov, O. Rossomakhina, N. A. Shishkina, E. Kolobanova, O. Malikhova, M. G. Abgaryan, M. Nikulin, P. Arkhiri, L. A. Vashakmadze, I. Peregorodiev, E. A. Suleimanov, I. Stilidi","doi":"10.18027/2224-5057-2023-13-4-7-17","DOIUrl":"https://doi.org/10.18027/2224-5057-2023-13-4-7-17","url":null,"abstract":"Introduction: The main current approach to the treatment of patients with resectable cancer of the stomach and gastroesophageal junction (GEJ) is perioperative FLOT chemotherapy. The mFOLFIRINOX regimen has been shown to be effective and safe in disseminated adenocarcinoma of the stomach and GEJ. This article presents preliminary results of the efficacy and safety assessment of perioperative FOLFIRINOX chemotherapy in patients with resectable cancer of the stomach and gastroesophageal junction.Materials and Methods: The FOLFIRINOX / FLOT study is a phase 2 / 3 open-label, randomized trial. Study enrollment was started in January 2019 and is currently ongoing. The inclusion criteria are: histologically confirmed resectable adenocarcinoma of the stomach or gastroesophageal junction, Siewert types II–III, clinical stage cT4aN0M0, cT1–4N1–3M0 or cT2–4N0–3M0, with total or subtotal involvement of the stomach. The following regimens were used for perioperative chemotherapy: FLOT — docetaxel 50 mg / m2 on day 1, oxaliplatin 85 mg / m2 on day 1, leucovorin 200 mg / 2 on day 1, 5FU 2600 mg / m2 × 24 hours starting on day 1, or mFOLFIRINOX — irinotecan 180 mg / m2 on day 1, oxaliplatin 85 mg / 2 on day 1, leucovorin 200 mg / m2 on day 1, 5FU 250 mg / m2 bolus on day 1 and then 2200 mg / m2 × 48 hours on day 1. The primary endpoint was 5‑year overall survival.Results: All planned preoperative courses of chemotherapy had been administered to 25 (86 %) patients in the FLOT group (n = 29) and 22 (92 %) patients in the FOLFIRINOX group (n = 24). Four (12 %) and 2 (8 %) patients in the FLOT and FOLFIRINOX groups, respectively, discontinued the treatment. The surgical staging was used in 48 patients (91 %) (25 [86 %] in the FLOT group and 23 [96 %] in the FOLFIRINOX group). Complete tumor regression (Mandard grade 1) had been achieved in 4 patients (2 [7 %] in the FLOT group and 2 [8 %] in the FOLFIRINOX group). Postoperative complications were detected in 2 patients (8 %) in the FLOT group and 4 (17 %) in the FOLFRIRNOX group. Thirty-three patients (62 %) received all scheduled postoperative treatment courses (n = 19, 66 % for FLOT and n = 14, 58 % for FOLFIRINOX).Conclusions: The preliminary results of the FOLFIRINOX / FLOT study showed comparable tolerability of the regimens and comparable complete pathological response rates. However, there was a higher incidence of postoperative complications detected among patients who received the FOLFIRINOX regimen compared to the FLOT group.","PeriodicalId":513023,"journal":{"name":"Malignant tumours","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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