Vol 24, No 1 (2022)
CLINICAL ONCOLOGY
The biobank of the National Medical Research Centre for Oncology as a resource for research in the field of personalized medicine: A review
Abstract
Biobanks are the platform for innovative biomedical research in the field of translational and personalized medicine. The important aspect for conducting large-scale research in the field of genomics, transcriptomics, proteomics is the availability of a sample information of the documented high-resolution samples. The biobanks solve the problem of forming groups of patients with different nosology within the population of interest and provide clinical and laboratory information on each sample. The aim of this article is to describe the Biobank processes of the National Medical Research Centre for Oncology within the framework of existing projects and build up collections. The review discusses the main stages of the systematized biobank process, describes the methods of sample preparation of different types of biological material, and also provides statistics of the build up collections. To this date, the predominant part of the depository consists of tissue samples of patients diagnosed with colorectal cancer 24% and stomach cancer 23% of the total number of tissue samples, while the number of tissue samples of pancreatic cancer is 10%, and esophageal cancer and breast cancer – 22%. In addition to tissue samples, the biobank of the National Medical Research Centre for Oncology stores 24 cell lines of a human origin and the collection of 200 microbiota samples: 100 are from patients diagnosed with lung cancer and 100 from conditional healthy donors. Currently, the studies have been performed on biomaterial from the biobank build up collections to search for prognostic biomarkers and potential targets for targeted therapy by using high-throughput sequencing in patients diagnosed with pancreatic cancer and brain cancer. Thus, the collections play an important role for research in the field of personalized medicine, providing early diagnosis and effective treatment for each patient.
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Clinical and morphological features of breast tumors with PIK3CA mutations in Russian patients: Observational study
Abstract
Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,25–40% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced.
Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC.
Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fisher’s exact test. The age at diagnosis in patients with different PIK3CA status was compared using the Mann–Whitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the Cochrane–Armitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013).
Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found.
Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.
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Management of patients with hormone receptor-positive HER2-negative metastatic breast cancer: data of randomized trials and real-world evidence
Abstract
The Satellite Symposium of Novartis Pharma was held on January 28th,2022, within the framework of the RUSSCO Big Conference "Breast Cancer". It was dedicated to the diagnostics and treatment of patients with hormone receptor-positive HER2-negative advanced breast cancer (HR+/HER2- aBC). The information concerning two new observational studies was showed during the symposium: the retrospective analysis of the sequence of BC patients’ treatment in Moscow and the PROSPERITY study. The preliminary results of the data analysis concerning Moscow patients with breast cancer indicated the widespread practice of using endocrine therapy as an early-line treatment for HR+/HER2- aBC. Special attention was paid to new data concerning the use of Piqray (alpelisib) for the treatment of HR+/HER2- aBC with a PIK3CA mutation. The review of new results obtained in clinical trials and in clinical practice of the Loginov Moscow Clinical Research Center (Moscow) was made. The obtained data results indicate that alpelisib in combination with fulvestrant is effective after disease progression on CDK4/6 inhibitors, regardless of the duration of prior CDK4/6i therapy, as well as in patients who previously received fulvestrant. The duration of alpelisib treatment can be prolonged due to the competent approach to prevent and to control the adverse events.
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Assessment of the impact of the use of durvalumab for the treatment of advanced small cell lung cancer on the achievement of the target "reduction in mortality from neoplasms"
Abstract
Aim. Impact evaluation of effective methods for advanced small cell lung cancer treatment using the drug durvalumab on the achievement of the Russian Federation national and regional programs “Healthcare Development” target indicator “reduction of mortality from neoplasms”.
Materials and methods. The methodology of this study is based on general scientific research methods: general logical (analysis, synthesis, induction), theoretical (generalization), empirical (description, calculation, measurement, comparison). The regulatory framework of the research work was made up by the legislation of the Russian Federation, documents regulating the procedure for providing medical care to patients with malignant neoplasms, technical regulation norms enshrined in the documents of the national standardization system that regulate the procedure for health technologies assessment. As an empirical base, the available official data on the epidemiology of lung cancer, Russian and foreign scientific publications, Russian clinical guidelines for the diagnosis and treatment of malignant neoplasms of lungs were analyzed. To conduct health technologies assessment, a mathematical model was developed based on Microsoft Excel 2019 software. The mathematical apparatus used to create a predictive model adapted to predict the results of healthcare cancer programs at the federal and regional levels.
Results. The use of durvalumab for the treatment of advanced small cell lung cancer will provide an increase in the achievement of the target indicator “reduction of mortality from neoplasms” of the national program “Healthcare Development” in 2022 by 21.3% (499 additionally prevented deaths), in 2023 by 7.0% (366 additionally averted deaths), in 2024 by 6.0% (441 additionally averted deaths). Obtained results show that the use of durvalumab in combination with standard chemotherapy in patients with advanced small cell lung cancer can have a significant impact on the achievement of targets set in healthcare cancer programs.
Conclusion. The durvalumab usage in real practice in combination with standard chemotherapy (etoposide + platinum drug), in comparison with the use of only standard chemotherapy (etoposide + platinum drug), will reduce cancer mortality and will contribute to achieving the targets of the Russian Federation national and regional programs “Healthcare Development” “reduction of mortality from neoplasms”.
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Osimertinib and routine practice: the experience of the drug application in different clinical situations in case of metastatic non-small cell lung cancer with an EGFR mutation. Case report
Abstract
After the introduce of new treatment options is always important to see how the results of the registered studies will be putted into routine clinical practice. Clinical studies help to assess the efficacy and safety of therapy and to conduct the objective comparison of the current standard of treatment. However, it is impossible to take into account all the variety of situations that oncologists can face in their daily work. Nowadays, the use of targeted therapy in the presence of the specific genetic disorders, in particular, driver mutations in the epidermal growth factor receptor (EGFR) gene, is an integral part of the management of patients with advanced non-small cell lung cancer (NSCLC). The first EGFR tyrosine kinase inhibitors (TKIs) have significantly changed our possibility of the treatment in this group of patients, and today we are already using the third-generation EGFR TKIs. The review analyzes the experience of using the third-generation EGFR TKIs – osimertinib, through the prism of questions, asking by the practitioners: evaluation of the efficacy of treatment in routine practice, the management of difficult patients, in particular, the patients with bone and brain metastases, the patients with multiple primary tumors, the management tactics of patient taking into account the COVID-19 pandemic and related treatment interruptions. The literature and international experience review is completed by clinical cases from different regions of the Russian Federation.
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Atezolizumab in the first-line treatment of metastatic non-small cell lung cancer. Clinical experience of the drug application. Case report
Abstract
Background. Lung cancer is still the leading cause of cancer morbidity and mortality among both men and women. At the same time, non-small cell lung cancer (NSCLC) accounts for 85% of all cases of malignant tumors. Historically, the treatment for locally advanced and metastatic lung cancer was consisted of systemic cytotoxic therapy. The main aim was to destroy tumor cells, to reduce the severity of the disease manifestations, to improve the quality of life and to prolong survival. Recent discovery of mutations in the epidermal growth factor receptor (EGFR) gene and ALK translocations or proto-oncogene 1 (ROS1) has led to a paradigm shift and the development of molecularly oriented therapeutic agents and options, such as targeted therapy as well as immunotherapy using immune checkpoint inhibitors.
Aim. Present the efficacy of atezolizumab application in the first-line treatment of metastatic non-small cell lung cancer associated with high PD-L1 expression.
Clinical case report. A 64-year-old patient with T1N3M1 stage IV right lung cancer, brain and right adrenal metastases was under observation. Right supraclavicular lymph node biopsy was performed. The histological examination showed the metastases of squamous cell carcinoma. EGFR-activating mutations, ALK translocations and ROS1 were not detected (wild-type). The immunohistochemical analysis showed a high expression of programmed cell death ligand (PD-L1) – 90%. The patient was treated using atezolizumab 1200 mg every 21 days in monoregimen. The patient was receiving 50 injections of the drug for almost 3 years. The effect of the therapy was evaluated using hybrid 18-F-fluorodeoxyglucose PET/CT. The complete metabolic regression of the tumor was obtained after 14 cycles of treatment and was persisting throughout the treatment period for 36 months. Grade 2 neutropenia after 6,7 and 30 cycles of therapy was noted among the adverse effects. Immune-mediated adverse events were not described.
Conclusion. The application of atezolizumab in monoregimen can provide long-term overall survival in patients with untreated metastatic EGFR-negative, ALK-negative NSCLC associated with high PD-L1 expression, as well as a favorable safety profile and quality of life.
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Laparoscopic resections of the liver and the colon in patients with synchronous colorectal metastases: a case series
Abstract
Aim. To evaluate the results of laparoscopic simultaneous colorectal and liver resections in patients with synchronous liver metastases.
Materials and methods. From July 2019 to July 2021 9 patients with synchronous liver metastases of colorectal origin underwent one-stage mini-invasive surgery in the Department of Oncology №4 City Clinical Oncological Hospital №1. There were 4 totally laparoscopic procedures while 5 patients had laparoscopic colon resection and an open hepatectomy. A laparoscopic rALPPS right hepatectomy with sigmoid colon resection was performed in one case.
Results. There were no deaths during hospitalization or within 90 days after surgery. There were no severe complications requiring repeated surgeries or long-term intensive therapy (Dindo–Clavien IIIB–IVB grade). Two patients needed an ultrasound-guided drainage of hematoma and biloma, respectively. There was one case of grade A of liver failure and one case with prolonged antibacterial therapy caused by unclear fever. The average duration of interventions was 401±121 min, the average volume of blood loss was 383±331 ml. Mean post-operative hospital stay was 10±4 days.
Conclusion. Our initial experience in the implementation of one-stage laparoscopic surgery in the treatment of patients with synchronous liver metastases of colorectal origin is promising and requires further research and analysis of long-term results.
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Therapy of lymphoproliferative diseases in the era of COVID-19: challenges and solutions
Abstract
On January 20,2022, the symposium "Therapy of lymphoproliferative diseases in the era of COVID-19: difficulties and solutions" was held. It was organized by the Russian Society of Oncohematologists. At the symposium, the experience of the hematology service of City Clinical Hospital №52 of Moscow was discussed, as well as changes in international clinical guidelines for managing patients in conditions of COVID-19 based on a review conducted by the European Hematology Association (EPICOVIDEHA).
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Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study
Abstract
Aim. To assess effectiveness and safety of Extimia® BIOCAD (INN: empegfilgrastim) used to decrease the rate and duration of neutropenia, the rate of febrile neutropenia and infections that manifest in febrile neutropenia in patients with lymphoproliferative diseases who receive myelosuppressive therapy.
Materials and methods. The paper presents the results of the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study of effectiveness and safety of Extimia® BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases who receive cytotoxic therapy. The second stage of the interim analysis describes patient characteristics, therapy used in 221 patients with morphologically confirmed lymphoma who received one or more cycles of chemotherapy as part of LEGERITY study. The endpoints of interest included the rate of Grade 3/4 neutropenia in patients, after the first cycle of any therapy line; the rate of febrile neutropenia; the rate of Grade 3/4 infectious complications; the rate of antibacterial therapy prescriptions; and the assessment of the relative dose-intensity of received chemotherapy. Additionally, the incidence rate of all adverse drug reactions (ADRs) was assessed in patients who received at least one dose of the study drug; the incidence rate of all serious ADRs was assessed in patients who received at least one dose of the study drug; the incidence rate of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 3/4 ADRs – in patients who received at least one dose of the study drug; the rate of study drug discontinuations due to ADRs was also assessed.
Results. As of the second interim analysis, LEGERITY included 221 patients with various indolent and aggressive lymphomas. Median age of the patients was 53 years (19–82). A group of older patients (over 60 years of age) accounted for 34% of the study population. Patients received ≤1 injection of Extimia per chemotherapy cycle. Grade 3/4 neutropenia was registered in 6.7% (n=14) patients. Overall, all-grade neutropenia was reported in 21.4% (n=44) patients. Febrile neutropenia was reported in 2.9% cases. Severe infections and the use of antimicrobials were reported in no patients throughout the CT period and after each cycle of therapy. Most commonly reported adverse reactions included mild-to-moderate ossalgias (6.8%) and myalgias, back pain, and arthralgias (3.2%), that did not require pharmaceutical therapy. One (0.5%) patient had a severe adverse drug reaction – a CTCAE 5.0 Grade 4 hypotension episode.
Conclusion. Interim analysis results support high effectiveness and safety of the Russian original pegylated granulocyte colony-stimulating factor of empegfilgrastim (Extimia®) in patients both with indolent and aggressive lymphomas. Real world evidence demonstrates a favourable safety and tolerability profile of empegfilgrastim in all age groups, including in the aging population. As of the moment of the interim analysis publication, the study is ongoing. Final conclusions on the safety and effectiveness of empegfilgrastim (Extimia®) are to be drawn upon the study completion.
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Immuno-morphological characteristics of bone marrow in patients with ovarian cancer
Abstract
Background. Nowadays, one of the promising areas is the study of bone marrow in malignant tumors. It is known that hematogenous metastasis to the bone marrow in cancer is a common event. Identification of bone marrow lesions in ovarian cancer, as well as the study of hematopoiesis, can provide additional information about the features of metastasis of this tumor and will make it possible to assess the prospects for targeted therapy.
Aim. To assess the possibility of detecting disseminated tumor cells in the bone marrow in patients with ovarian cancer, to establish the frequency of bone marrow damage and to analyze the relationship with the clinical and morphological parameters of the tumor.
Materials and methods. This work includes 42 patients with ovarian cancer who received treatment at the Blokhin National Medical Research Center of Oncology. The study was carried out by morphological and immunological methods. Morphological examination of the bone marrow (counting myelograms, calculating myelogram indices, detection of tumor cells) was performed by two morphologists. Disseminated tumor cells were detected using flow cytometry (FACS Canto II, USA, Kaluza Analysis v2.1 software). Monoclonal antibodies were used: CD45, EPCAM.
Results. Disseminated tumor cells in the bone marrow of patients with ovarian cancer were determined based on the expression of the EPCAM antigen and lack of expression of CD45 antigen. Disseminated tumor cells were found in 65.2% (n=15)of bone marrow aspirates. Disseminated tumor cells did not correlate with tumor size, lymph nodes status and stage. The frequency of bone marrow damage was higher at stage III and reached 78.6% (11 out of 14 patients), while it was 33.3% (1 of 3 patients) in stage I. 40.0% of positive cases (2 out of 5 patients) were detected at stage IV. Disseminated tumor cells were found in 78.6% (n=11) of bone marrow aspirates in primary ovarian cancer, while in recurrent ovarian cancer they were found only in 44.4% (n=4).
Conclusion. The hematogenous dissemination of ovarian cancer in the bone marrow was established. Bone marrow lesions was noted even in the early stages of the tumor process. The frequency of detection of disseminated tumor cells in the bone marrow of patients with ovarian cancer was 65.2%. More frequent bone marrow damage was noted in primary ovarian cancer. The number of myelocytes was significantly lower in primary ovarian cancer without bone marrow damage. The number of lymphocyte was lower in cases of bone marrow lesions.
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Comprehensive rehabilitation of cancer patients: A review
Abstract
Due to the improvement of the results of combined treatment of malignant tumors the survival rate of cancer patients is increasing. The issue of improving the quality of life, both during treatment and after its completion, is becoming more and more urgent. Conducting an individually selected comprehensive rehabilitation treatment conducted by a multidisciplinary team aimed at correcting not only medical problems but also the social capabilities of the patient taking into account the personal experience of the patient, his psychological traits, habits, etc., helps reduce the number of complications significantly, improve the quality of life of patients. The article discusses the stages, methods of rehabilitation, nutritional support for cancer patients.
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Factors associated with the degree of 99mTc-MIBI accumulation in parathyroid glands neoplasms during planar scintigraphy and SPECT/CT in primary hyperparathyroidism
Abstract
Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease, after diabetes mellitus and thyroid gland disorders. Surgical removal of the hyperfunctioning parathyroid glands is the only radical treatment. Various methods of preoperative imaging and intraoperative navigation are developed. Planar scintigraphy with 99mTc-MIBI is used for visualization and it is the most frequently performed radionuclide study in PHPT, while it has a relatively low sensitivity and specificity. SPECT/CT can reduce false-negative and false-positive results, and combines the advantages of radionuclide diagnostic methods and computed tomography. However, the factors that prevent the accumulation of 99mTc-MIBI in patients with PHPT are not clear enough.
Aim: To identify the factors associated with the degree of accumulation (uptake rate) of 99mTc-MIBI in the parathyroid glands during planar scintigraphy and SPECT/CT.
Materials and methods: The cross-sectional comparative study included 186 patients with PHPT who underwent planar scintigraphy and SPECT/CT for topical diagnosis of parathyroid glands and minimally invasive parathyroidectomy (MIP) followed by histological and immunohistochemical examination of parathyroid glands. The patients were divided into 3 groups depending on the accumulation of 99mTc-MIBI. The accumulation of 99mTc-MIBI was assessed by the expert as low-, moderate-, and high-intensity.
Results: The association between the volume of the parathyroid glands on ultrasound and the intensity of the capture of the radiopharmaceutical was revealed, and 80% of low uptake is observed if volume is less than 0,215 cm3 (it corresponds to the linear size of the parathyroid gland ≤5 mm). Next factor that complicate the interpretation of the results of planar scintigraphy and SPECT/CT in patients with PHPT is thyroid diseases. The associations of the level of PTH, calcium in the blood, the localization and cellular composition of the parathyroid glands, the index of proliferative activity (Ki67), the expression of PTH, P-glycoprotein, cyclin D1 in the PTG tissue with the intensity of 99mTc-MIBI accumulation were not found.
Conclusions: The main factor that positively associates with the degree of 99mTc-MIBI accumulation with planar scintigraphy and SPECT / CT is the volume of the parathyroid glands according to ultrasound data. Comorbidity of the thyroid gland has tendency to be associated with a negative result of radionuclide diagnostics, thus based on the ultrasound data of the thyroid and parathyroid glands it is possible to choose the second preferable method of imaging (SPECT/CT or contrast enhanced CT).
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Own Experience of Using Lenvatinib in Patients with Advanced Hepatocellular Carcinoma in Real Clinical Practice based on Moscow City Oncological Hospital №62
Abstract
Background. Hepatocellular carcinoma (HCC) (hepatocarcinoma) is the most common (about 85% of cases) malignant liver tumor originating from hepatocytes. According to officially published statistics for the city of Moscow for 2019,329 people were registered with the first-ever diagnosed C22 malignant neoplasms (liver and intrahepatic bile ducts, including 6.7% of those who were actively identified. The absolute number of such patients registered at the end of the year was 716, which is 5.7 per 100 000 of the population. The contingent accumulation index is 2.2 (the average for Russia is 1.5). With that,43.1% of patients had stage IV. Mortality rate during the first year after diagnosis is 53.9% (in Russia on the whole, this value is 66.5%). Drug systemic therapy is the method of choice for HCC which is not subject to surgical intervention and local methods of treatment.
Materials and methods. A retrospective analysis of the efficacy and safety of lenvatinib in patients diagnosed with HCC was carried out in real clinical practice at the Outpatient Oncology Care Center of the Moscow City “Oncological Hospital №62”. The data analysis covers the period from February 2016 to June 2021. The analysis included 15 patients with a morphologically verified diagnosis of HCC treated with lenvatinib. For the majority of patients,11 (73.3%) patients received lenvatinib as first-line therapy.
Results. The median progression-free survival was 11.2 months for the entire observation group. In the first line of therapy, the PFS result was the highest and amounted to 12.3 months. The median dose received by patients was 10.9 mg. The level of disease control was 86.6%. The most clinically significant adverse events were grade 2 neutropenia, grade 2 thrombocytopenia, grade 2 asthenia, grade 2–3 hypertension. Lenvatinib had a manageable safety profile.
Conclusion. The performed analysis confirms the data of the REFLECT study on the efficacy of lenvatinib both in healthy patients and in patients with a spectrum of comorbidities with significant (more than 50% of the liver parenchyma) liver damage.
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A modern approach to the treatment of cancer-associated venous thromboembolic complications: a lecture
Abstract
Cancer-associated venous thromboembolic complications are one of the main topical problems in the system of practical healthcare. Having overlapping pathogenetic mechanisms of development, thromboembolic complications accompany the oncological process and often act as its manifesting sign. Treatment of onco-associated venous thromboembolic complications is not an easy task, which is determined by the multiplicity of the pathogenetic mechanisms of hemostatic system disorders in the cohort of patients under consideration, who are threatened both in terms of the development of total PE and fatal bleeding. In addition to the features of the treatment phases, their duration, an important point in the treatment of cancer-associated thrombosis is a limited list of recommended drugs, as well as the permitted dosage regimens. The article analyzes the results of research aimed at studying the effectiveness of apixaban in the treatment of cancer-associated thromboembolic complications. Now the “gold standard” for the treatment of venous thromboembolic complications is dalteparin. However, low compliance in the use of dalteparin leads to premature termination of treatment or the patient's independent transition to alternative drugs. The appearance of direct oral anticoagulants has significantly changed the treatment paradigm in this morbid group of patients, while leaving a number of unresolved issues.
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Quality of life and overall survival are primary priorities of patients with advanced breast cancer: results of sociological research
Abstract
Background. Breast cancer is the most common cancer in women. Metastatic breast cancer is an incurable disease, the main treatment goals of which are to increase overall survival and improve quality of life.
Aim. To assess the priorities of patients with breast cancer in the framework of a sociological study.
Materials and methods. For the first time, the main results of a sociological study of patients diagnosed with breast cancer, conducted by the Interregional Public Movement "Movement Against Cancer" in October–November 2021. This analysis reflects the needs of patients with breast cancer in various regions of the Russian Federation. A total of 675 people were interviewed,662 questionnaires were allowed for analysis.
Results. In the rating of patients' desires regarding the results of treatment, regardless of the region and the duration of the course of the disease, the leading positions were taken by "improved quality of life" (46.2%) and "increased life expectancy" (46.4%). In the rating of preferences regarding the therapy received, the first place was taken by the value “It is important to maintain good health, working capacity and the ability to live a full life” (39.1%).
Conclusion. The priority for all patients diagnosed with breast cancer is an effective and safe treatment that will ensure a good health and performance and safe a high quality of life for a long time.
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NGAL and KIM-1 – early urinary biomarkers of nephrotoxicity mediated by cisplatin: Observational study
Abstract
Background. Cisplatin is widely used in modern oncological practice. Despite high efficacy treatment with cisplatin is conjugated with high risk of nephrotoxicity. Approximately one third of patients develop renal disfunction after first injection of cisplatin. In clinical practice serum creatinine elevation is used as a marker of renal damage, which is observed after failure of 50% of kidney function. That is why the finding of early biomarker of nephrotoxicity is still an issue. NGAL and KIM-1 are markers of renal damage, the predictive value of which has been described in cardiac surgery and resuscitation practice: an increase in the concentration of these markers in urine precedes the development of renal damage, both ischemic and direct toxic.
Aim. To evaluate the role of NGAL and KIM-1 in urine as early markers of cisplatin nephrotoxicity.
Materials and methods. The study included 50 patients treated with cisplatin in combination with fluoropyrimidines or paclitaxel. Prior to treatment and over a period of 8 weeks, the Friedman test was used to assess blood pressure, plasma creatinine, potassium, urea levels, daily proteinuria, urine NGAL and KIM-1 levels, and glomerular filtration rate (GFR). ROC analysis was used to assess the prognostic significance of NGAL and KIM-1 in the development of nephrotoxicity.
Results. There was a statistically significant increase in the level of urea (χ²=17.7; df 4, p=0.001), potassium (χ²=42; df 4, p<0.001), a decrease in GFR (χ²=32.3; df 4, p<0.001), the appearance of proteinuria (χ²=50.4; df 4, p<0.001). The concentration of NGAL and KIM-1 increased already one week after the start of cisplatin therapy, reaching a maximum by 8 weeks (χ²=200; df 4, p<0.001). The appearance of NGAL at a concentration of 10.743 ng/ml and KIM-1 at a concentration of 182.4 pg/ml in the first week after administration of cisplatin allows predicting the development of nephrotoxicity by the 8th week with high sensitivity (90.91%) and specificity (94.87%), AUC 0.96.
Conclusion. The appearance of NGAL and KIM-1 in urine already in the first week of treatment allows predicting the development of nephrotoxicity – a decrease in GFR of less than 60 ml/min by the 8th week of therapy with high sensitivity and specificity. Both biomarkers can be considered early prognostically significant.
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Nutritional support in the perioperative period of treatment of cancer patients: Retrospective cohort study
Abstract
Background. The most important component of multimodality treatment of cancer is nutritional support. The management of the correct full nutritional support in the perioperative period will help to maintain body weight and muscle function, to reduce the frequency of development of postoperative complication severity and to reduce hospital length of stay. To provide full nutritional support is necessary to cover all energy requirements in patients (30 kcal/kg body weight per day), protein requirements (1.5 g of protein/kg of body weight per day) and eicosapentaenoic acid requirements (2 g/day), applying clinical nutrition through the appropriate routes of administration (oral, enteral, parenteral or combined).
Materials and methods. The trial studied the dynamics of the nutritional status of 400 oncological patients who underwent surgical treatment at the Hertsen Moscow Oncology Research Institute – the branch of the National Medical Research Radiology Centre from 2019 to 2021. The patients were divided into 2 groups: the main (n=200) and the control (n=200). The patients of the main group received full nutritional support. The control group consisted of the patients, according to retrospective analysis of the patients, with the traditional approach to nutritional support. The study included patients with nutritional deficiency confirmed by clinical criteria, as well as patients with malignant neoplasms of the upper gastrointestinal tract – the gastrointestinal tract (esophagus and stomach), colon and rectum, as well as head and neck.
Results. The application of nutritional therapy in the perioperative period can improve the nutritional status of the patients with head and neck and upper gastrointestinal tract cancer (the statistically significant increase in body weight by 1 kgs and 0.5 kgs, respectively). In patients with colorectal cancer, body weight during the treatment was stable with the tendency to increase by 0.4 kg. Perioperative nutritional support for patients with head and neck and upper gastrointestinal tract cancer showed statistically significant increase of the level of both complete protein by 2.8 and 4.1 g/l, respectively, as well as serum albumin by 5.2 and 3.3 g/l, respectively. The absolute lymphocyte count increased at the trend level. No statistically significant difference was obtained during treatment in patients with colorectal cancer. Nutritional support in cancer patients during the surgical treatment allowed to reduce the total number of surgical complications by 36%, including the incidence of anastomotic failure by 3 times (p=0.014), infectious complications – by 1.5 times (p=0.074), to reduce the duration of stay in the intensive care unit, as well as inpatient stay in hospital to 0.3 and 1.08 bed days, respectively (p<0.05).
Conclusion. The application of nutritional support can help to reach more favorable perioperative course in cancer patients and also can lead to a decrease in the number of complications and early rehabilitation for patients, and on the other hand, will help to reduce the duration of stay in the intensive care unit as well as inpatient stay in hospital, reducing the cost of treating patients.
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PARP (Poly ADP‐Ribose Polymerase) inhibitors for locally advanced or metastatic breast cancer (Russian Translation of Cochrane Plain Language Summary)
Abstract
This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Taylor AM, Chan DLH, Tio M, Patil SM, Traina TA, Robson ME, Khasraw M. PARP (Poly ADP‐Ribose Polymerase) inhibitors for locally advanced or metastatic breast cancer. Cochrane Database of Systematic Reviews. Version published: 22 April 2021. DOI: 10.1002/14651858.CD011395.pub2
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Vascular endothelial growth factor (VEGF) targeting therapy for persistent, recurrent, or metastatic cervical cancer (Russian Translation of Cochrane Plain Language Summary)
Abstract
This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Chuai Y, Rizzuto I, Zhang X, Li Y, Dai G, Otter SJ, Bharathan R, Stewart A, Wang A; Vascular endothelial growth factor (VEGF) targeting therapy for persistent, recurrent, or metastatic cervical cancer; Version published: 04 March 2021; DOI: 10;1002/14651858;CD013348;pub2
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Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ФС 77 - 69203 от 24.03.2017 г.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 63964 от 18.12.2015 г.