Vol 24, No 6 (2022)


Cancer treatment and drug-induced QT interval prolongation: A review

Ostroumova O.D., Kochetkov A.I., De V.A.


Anticancer drugs can cause drug-induced prolongation of the QT interval. Prolongation of the QT interval is a known risk factor and an independent predictor of the development of life-threatening ventricular arrhythmias (polymorphic ventricular tachycardia, also called Torsades de Pointes), and sudden cardiac death in patients with and without structural heart disease. Healthcare practitioners should constantly evaluate the benefit/risk ratio prior to initiating treatment as well as continuing the chosen one. Some patients need particular attention, especially those who have risk factors such as comorbidities, taking drugs associated with QT interval prolongation, dehydration and electrolyte imbalance, etc. Despite apparent increase in the awareness among the patients and medical professionals, many scientists suggest that there is a lack of awareness about the true prevalence of these adverse events, which are at least 10 times greater than reported cases. This article discusses anticancer drugs that have an association with QT interval prolongation, and also possible strategies in the treatment of the patients with drug-induced QT interval prolongation.

Consilium Medicum. 2022;24(6):391-398
pages 391-398 views

A complex approach to continuous cardiac monitoring of neoadjuvant chemotherapy: Observational study

Buziashvili Y.I., Stilidi I.S., Asymbekova E.U., Matskeplishvili S.T., Artamonova E.V., Akhmediarova N.K., Sherstyannikova O.M., Akildzhonov F.R.


Background. Recent advances in targeted chemotherapy have led to improved outcomes in patients with breast cancer (BC) and reduced overall mortality. Neoadjuvant chemotherapy (NAC) is used to reduce the degree of invasion and dissemination in the body in cancer patients. The traditional approach of assessing serial echocardiography detects significant changes in left ventricular ejection fraction (LV EF) and provides limited predictive sensitivity and specificity for continuous cardiac monitoring. Algorithms for assessing the state of the cardiovascular system, proposed in the world literature, include the assessment of LV EF, tissue Doppler sonography, and the determination of serum biomarker levels. However, the use of this approach in clinical routine practice is limited due to low cost-effectiveness and awareness of physicians.

Aim. To conduct a comprehensive assessment systolic and diastolic function, deformity, myocardial tissue harmonics and levels of cardiac biomarkers as a tool for predicting and stratifying the risk of CAH.

Materials and methods. The prospective study included 72 patients with a confirmed diagnosis of BC during NAC, who underwent a comprehensive assessment of the cardiovascular system at the Bakulev National Medical Research Center for Cardiovascular Surgery, as a continuous cardiac monitoring in the period from March 2021 to February 2022, the average age of all patients was 47.9±11.9 years, the stages of the tumor process varied between I and IV. Clinical research methods included the collection of clinical and anamnestic data and sequential analysis of echocardiographic parameters and the level of serum biomarkers. All patients underwent 2D and M-mode echocardiography, pulsed wave Doppler to determine the velocity of blood flow through the mitral valve and TD for the right and left ventricles in accordance with the recommendations of the American Society of Echocardiographers (ASE). LV systolic and diastolic function was assessed according to the ASE clinical guidelines. Peak longitudinal deformation of the LV and the left atrium in various projections was analyzed using the Qlab workstation (Philips Qlab, version 10.5, CMQ; Philips Healthcare, Bothell, Washington, USA). Serum levels of cardiac biomarkers such as brain natriuretic peptide (NT-proBNP) and ST-2 protein (growth stimulating factor) were also analyzed. Fasting blood was used to determine the level of soluble ST-2 and NT-proBNP before NAC, at the intermediate and final stages. Soluble ST-2 was measured using ELISA (R/D Systems, Minneapolis, Minnesota) and NT-proBNP using electrochemiluminescent immunoassay (Elecsys proBNP, Roche Diagnostics, Indianapolis, Ind.) according to the manufacturer's instructions.

Results. In our study, we assessed early changes in the LV myocardium during NAC in patients with BC. As can be seen from the figure, the level of both markers begins to increase already during NAC with a subsequent increase after the end of therapy. Thus, NT-ProBNP increased from 74.4±25 pg/ml to 98.9±22 pg/ml at the intermediate stage and to 110.7±21 pg/ml at the final stage. ST-2 increased from 25±4.5 ng/ml to 29±3 ng/ml (p=0.00001) and 31±3 ng/ml. In some patients (24%), at the final stage of the examination, the level of NT-proBNP had pathological values and exceeded 124 pg/ml. The situation is different with LV EF – which in group 1 decreases by 11%, and in group 2 by only 6%, but nevertheless significantly. Indicators of LV diastolic function suffer on the background of taking NAC, the main indicators that increased after NAC were the volumes of the left atrium in both groups, the E/A ratio and the systolic filling fraction. Early diastolic lateral wall velocity significantly decreased only in the group with an excessive increase in NT-proBNP after NAC. For other indicators, there was a trend of deterioration in diastolic function. The results of changes in the parameters of LV and left atrium myocardial deformation before and after NAC are also presented. We observe a significant deterioration in overall myocardial deformity and deformity in various positions after NAC. In the analysis of serum biomarkers, the percentage increase in NT-proBNP correlated with the deterioration of LV EF (Spearman coefficient -0.34). A deterioration in the NT-proBNP biomarker of more than 10% has a prognostic value of severe NAC cardiotoxicity with χ2=7.17. With multiple regression, a model was obtained where the combination of the following indicators had statistical significance. The degree of change in the other marker ST-2 had significant correlations with the degree of change in CSR, LA volume, total longitudinal strain, strain and strain rate in 4- and 2-chamber studies, as well as LA strain rate. All 72 patients with BC initially had intact LV systolic function before NAC. During NACT, at the stage of the interim study, an increase in the CSR index was noted (p=0.02 compared with the outcome), immediately after the end of the NACT course, further progression of the CSR index was observed (p=0.006 compared with the initial value). EF at the interim study decreased by 4.5% and after the end of NAC by 8.3%.

Conclusion. Based on our results, taking into account the entire patient population, NAC undoubtedly causes changes in systolic and diastolic function, a decrease in wall velocity and LV and LA myocardial deformity, and an increase in serum biomarkers. The most sensitive and specific marker of subclinical LV myocardial dysfunction is indicators of diastolic function and deformation of the LV and LA myocardium, as well as the level of serum biomarkers – NT-proBNP and ST-2. The variety of clinical manifestations of cardiotoxicity, the long latency period and the progressive nature of the disease emphasize the need for early screening and long-term follow-up of patients after chemotherapy. This algorithm for comprehensive assessment of the cardiovascular system can become a more widely used non-invasive method and an effective tool in predicting a high risk of cardiotoxicity.

Consilium Medicum. 2022;24(6):399-407
pages 399-407 views

Rituximab-induced interstitial pneumonitis in patient with non-Hodgkin lymphoma: a clinical case

Ognerubov N.A., Antipova T.S.


Rituximab is a chimeric monoclonal antibody against CD20+ lymphocytes used to treat non-Hodgkin lymphoma, hematological and autoimmune diseases – rheumatoid arthritis, systemic lupus erythematosus, thrombocytopenic purpura, hemolytic anemia, multiple sclerosis. The safety of the drug is critical to the choice of treatment. Rituximab-associated interstitial lung disease is rare.

Objective. To describe a case of interstitial pneumonitis induced by rituximab in monotherapy at the end of maintenance therapy.

Materials and methods. We describe a case of a 37-year-old patient with stage IIB non-Hodgkin lymphoma involving palatine tonsils and cervical and submandibular lymph nodes on both sides. Histologically, this tumor was a diffuse large B-cell lymphoma.

Results. A patient received six R-CHOP courses of chemotherapy and immunotherapy for stage IIB diffuse large B-cell lymphoma. After the therapy, a complete clinical and metabolic response was achieved. Rituximab maintenance therapy was administered at a dose of 375 mg/m2 every 2 months for 2 years. At this treatment stage, combined positron emission tomography and 18F-fluorodeoxyglucose computed tomography (PET/CT with 18F-FDG) was performed at 4–5 months intervals. No radiological signs of pulmonary diseases were detected. Seven weeks after the last dose of rituximab (24 months), another PET/CT with 18F-FDG showed radiological changes that were considered to be interstitial pneumonitis, with no respiratory signs of the disease. No signs of tumor progression were found.

Conclusion. Rituximab may contribute to late pulmonary toxicity presented as interstitial pneumonitis in non-Hodgkin lymphoma patients at a young age after maintenance therapy for 24 months. PET/CT with 18F-FDG is the primary method of diagnosing pulmonary toxicity.

Consilium Medicum. 2022;24(6):408-411
pages 408-411 views

Personalized approach in the treatment of thyroid cancer: A review

Radzhabova Z.A.


The main goal is to improve treatment outcomes of disseminated inoperable thyroid cancer through a personalized choice of targeted agents. Considering gene mutations in drug choice will further improve the survival of patients with rare mutations. Despite the small sample of patients, mutation detection, regardless of localization, and basket studies will allow future results to be obtained much faster than in a dozen years and use these results in this rare category of patients. Basket studies allow patients with rare disorders to receive personalized therapy according to mutations in tumor tissue, regardless of the affected organ.

Consilium Medicum. 2022;24(6):412-415
pages 412-415 views

Endocrine side effects during cancer treatment. Lecture for practitioners

Glibka A.A., Mazurina N.V., Troshina E.A.


Targeted therapy and immune checkpoint inhibitors (ICI) are increasingly being used to treat many solid tumors. The use alpelisib and ICPI has a risk of side-effects, particularly endocrine dysfunctions. In this lecture, there are clearly stated: initial screening, monitoring, selection of therapy and emergency situations for each endocrinopathy, i.e. hyperglycemia during treatment with alpelisib and destructive thyroiditis and hypophysitis during treatment of ICI.

Consilium Medicum. 2022;24(6):416-421
pages 416-421 views

Cancer-associated thrombosis during chemotherapy: treatment and prevention: A review

Koroleva I.A., Kopp M.V.


Cancer-associated thrombosis is a significant problem today for both oncologists and vascular surgeons. In patients with malignant neoplasms the incidence of symptomatic venous thromboembolism (VTE) is 4–7 times higher than in the general population. The presence of distant metastases in solid tumors increases the risk of VTE. Most often, VTE develop in pancreatic cancer and stomach cancer. Chemotherapy increases the risk of developing VTE. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients with chemotherapy. The results of the СARAVAGGIO study demonstrated that apixaban is not inferior to dalteparin in the treatment of VTE in patients with active cancer and does not increase the risk of bleeding. Before starting chemotherapy, it is necessary to assess the risk of developing VTE using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score >2 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis with low molecular weight heparin. The idea of using direct oral anticoagulants seems promising, but so far it is beyond the scope of approved indications.

Consilium Medicum. 2022;24(6):422-428
pages 422-428 views

Massive blood loss in surgery for renal cell carcinoma associated with inferior vena cava tumor thrombus: Observational study

Feoktistov P.I., Shin A.R., Prikhodchenko A.O., Feoktistova E.N., Vyatkin P.V.


Background. An effective treatment for renal cell carcinoma complicated by tumor thrombus (TT) is nephrectomy with thrombectomy (NETE) from the inferior vena cava (IVC), which is associated with massive blood loss, high morbidity and mortality. The study aims to evaluate the infusion-transfusion protocol (ITP) for NETE from the IVC without extracorporeal circulation.

Materials and methods. The observational single-center study included 682 patients who were operated for NETE for renal cell carcinoma with TT. Patients were divided into 3 groups depending on the level of TT according to the Mayo classification. The InfraHepatic (InH) group included patients with TT levels I and II, the RetroHepatic (RH) group included patients with TT level III, and the SupraDiaphragmatic (SD) group included patients with TT level IV. Own concept of moderately advanced infusion in the amount of 130–140% of all losses were introduced. Qualitative and quantitative composition of ITP, frequency of use of sympathomimetics, complications and mortality were assessed.

Results. The rate of massive blood loss was 46.9% in the InH group, 74.7% in the RH group, and 86.3% in the SD group. ITP was characterized a significant increase in the absolute values of all infusion media, a decrease the proportion of crystalloids and colloids, an increase the proportion fresh frozen plasma, donated erythrocytes, and proportion of auto-erythrocytes between groups. The frequency of using intraoperative cell salvage in the InH group was 39.6%, in the RH – 67.7%, in the SD – 90.7%. The greatest hemodynamic shifts were recorded in the SD group. The frequency of postoperative complications was 24.3%, and hospital mortality was 7% with accordance to the ITP, adequate hemodynamic and laboratory monitoring in NETE. Low mortality due to hemorrhagic shock in our study (0.15%) emphasizes the effectiveness of the presented ITP.

Conclusion. The obtained data demonstrate the results of NETE as comparable with those presented in the available literature.

Consilium Medicum. 2022;24(6):429-434
pages 429-434 views

Dermatological toxicity of acute lymphoblastic leukemia treatment by protocol ALL IC-BFM 2002

Valiev T.T., Belysheva T.S.


Background. Аcute lymphoblastic leukemia (ALL) in children is not only the most common but also potentially curable disease in 85–90% cases. The other side of high effectiveness of modern treatment protocols – their toxicity. Inspite of skin and mucosal toxicity is not a life threatening condition, it requires a supportive care to prevent infectious complications, which prolong hospitalization, administration of antibacterial, antifungal and in some cases antiviral drugs.

Aim. To study skin and mucosal toxicity in patients with ALL, treated by ALL IC-BFM 2002 protocol.

Materials and methods. One hundred and nineteen pediatric patients with primary diagnosed ALL were enrolled the study. All the patients were treated by ALL IC-BFM 2002 protocol. Toxicity assessment was performed on each step by the scale of National Cancer Institute (NCI) USA, 2d version.

Results. The most often variants of skin and mucosal toxicity during ALL IC-BFM 2002 protocol were found on protocol mM/M, based on high-dosed methotrexate. In 42.1% stomatitis 2st. was diagnosed on methotrexate dose 5000 mg/m2, 3st. – 15.8%, 4st. – 5,3%. Methotrexate dosed 2000 mg/m2 coused stomatitis 3 st. in 6.3%, in other patients stomatitis was 1–2st. Exfoliative dermatitis was in 1 (1%) case with prolonged methotrexate elimination. Block polychemotherapy used in high risk group of patients was complicated with stomatitis 3–4 st. in 90%. In 20% naso-gastral catheter was performed and in 25% used partial/hole parenteral nutrition support. Alopecia was reversible and observed in 100% patients. Protocols I, II and maintenance treatment were free of clinically significant skin and mucosal toxicity.

Conclusion. The skin and mucosal toxicity profile of ALL IC-BFM 2002 protocol was tolerable. Hole volume of supportive care, preventing and treatment of dermatological toxicity of chemotherapy can prevent of severe skin and mucosal toxicity (soft tissue infections, sepsis, metabolic disorders).

Consilium Medicum. 2022;24(6):435-439
pages 435-439 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies