Klinicka Onkologie最新文献

Commentary on the newly released European Society for Medical Oncology (ESMO) guidelines for the diagnosis and treatment of metastatic colorectal cancer (mCRC). After 6 years, individual chapters have been updated, from molecular tumor testing to diagnostic and treatment procedures to the implementation of newly registered medicinal products. The authors highlight the most important changes in the guidelines. Awareness of possible new treatments for mCRC is important to determine the treatment strategy for patients with mCRC. In this commentary, we focus primarily on the status of systemic treatment in unresectable disease.

Background: The treatment of aggressive multiple myeloma (MM) patients, resistant to several treatment modalities, is very difficult in the real-world-evidence conditions. Ixazomib is a second-generation oral proteasome inhibitor. In combination with lenalidomide and dexamethasone, it is an effective and low-toxic treatment regimen for patients with relapsed or refractory MM.

Observation: The presented case reports of two patients with an aggressive course of MM demonstrate the surprising effectiveness of this regimen.

Conclusion: Repeated treatment with a combination of proteasome inhibitors (ixazomib) and immunomodulatory drugs (lenalidomide) may lead to significant clinical benefit in some patients and should be considered even in end-stage disease patients.

Background: During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients treated with acute coronavirus disease 2019 (COVID-19) in intensive care units (ICU) have suffered from neuropsychiatric complications such as anxiety, depression, and confusion. Conditions related to the environment have the potential to worsen these symptoms. In combination with virus-dependent neuroinflammation, they form a "toxic" mixture. Discussion and planning strategies for providing psychological care in the ICU during the pandemic have revealed a great current challenge.

Case series: We share our experience concerning psychological interventions for oncological patients with oxygen saturation depletion. Our observation of two SARS-CoV-2 patients suggests a close time-related association between the increase in inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) and intensive anxiety in the fast development of breath shortening in acute COVID-19 infection due to brain hypoxia and potential neuroinflammation.

Conclusion: As cytokine IL-6 regulates induction of CRP gene expression, the changes in IL-6 concentrations associated with anxiety symptoms and breath shortening in the observed cluster can be detected hours earlier than changes in CRP levels, with a diagnostic implication for the clinicians. The SARS-CoV-2 patients with oncological diseases treated in our ICU asked for personal bedside contact with clinical psychologists, considered it irreplaceable and reported this psychological care as beneficial.

Background: The aim of the study was to investigate the concentration of interferon (INF) -a, INF- g, interleukin (IL) -6, and secretory IgA (sIgA) in saliva during various regimens of antitumour treatment and immunotherapy (IT) with a/b-defensins in patients with cancer of the oral cavity and oropharynx in order to find ways to increase the effectiveness and improvement of the tolerability of antitumour treatment on the base of the identification of biomarkers for the evaluation of the antitumour effect and the prediction of complications.

Materials and methods: We have studied the changes in the immunity indices of 105 patients who were diagnosed with squamous cell carcinoma of the oral cavity or oropharynx for the first time. The patients received radiotherapy (RT) or chemoradiotherapy and IT with a/b-defensins in different doses (40 and 60 mg) at the 1st phase of the special treatment.

Results: A determined drop in the concentration of INF-a after cytostatic treatment, and the additional use of IT with a/b-defensins in different doses do not produce the protective effect on the production of INF-a. Regarding INF- g, a more than two-fold decrease in the concentration of INF- g in the saliva of patients in group receiving a double dose of an immunotherapeutic agent along with radiation therapy (RT) was noted, which may indicate an adjuvant effect of a/b-defensins in relation to RT, enhancing its antitumour influence, and thereby ensuring the regression of neoplasia. In case of an increased dose of a/b-defensins use during RT, there was found immunomodulatory effect in relation to IL-6. In the group of patients who received RT and a higher dose of the immune agent, the "scissors phenomenon" was noted - a simultaneous decrease in the concentration of INF- g and an increase in the concentration of sIgA in saliva, which, taking into account the reduced risk of mucositis and better regression of the tumour, shows the meaningful adjuvant and immunomodulating effects of a/b-defensin therapy in the study group.

Conclusion: High-dose IT with a/b-defensins against the background of cytostatic therapy in patients with cancer of the oral cavity and oropharynx potentially leads to an adjuvant and immunomodulatory effect with a decrease in the concentration of INF- g and a parallel increase in the concentration of sIgA in saliva, i.e., reconstruction of the immune response from Th1- to Th2-profile - the profile associated with the tumour regression. With the development of the radio-induced mucositis in these patients, a decrease in concentration of sIgA in saliva with a tendency to a progressive decrease of this index with the increase of mucositis severity was noted. The data obtained allow us to consider INF- g and sIgA as biomarkers of the effectiveness of traditional anticancer therapy during the use of a/b-defensins, and sIgA as a biomarker of the risk of developin

Background: The fundamental difference between tumor and normal tissue growth is the emergence of the microenvironment with diminished or extinguished immunogenicity. One of the main functions of oncolytic viruses is the formation of such a microenvironment, which leads to a revival of immunological processes and loss of viability of cancer cells. Oncolytic viruses are being continuously improved and should be considered as a possible adjuvant immunomodulatory cancer treatment. A key requirement for the success of this cancer therapy is the specificity of the oncolytic viruses, which replicate only in tumor cells but do not affect normal cells. In this review, optimization strategies to achieve cancer specificity with increased efficacy are discussed and the most interesting results from preclinical and clinical trials are presented.

Purpose: This review provides information on the current status of the development and use of oncolytic viruses as part of the bio-logical treatment of cancer.

Background: Malignant lymphomas represent a highly heterogeneous group of tumors with varied clinical behavior - from indolent to very aggressive forms with survival in the order of months. From the very beginning, these diseases are considered systemic, often occurring in several anatomical locations simultaneously. However, diagnosis and exact classification are usually inferred from a bio-psy of a single pathological lymph node or infiltrate, even though clinical experience shows that the bio-logical behavior of lymphoma is not necessarily identical across anatomical locations. In an effort to address this issue as well as the problem of bio-psy of not easily accessible compartments, circulating free DNA (cfDNA), which contains circulating tumor DNA (ctDNA) released from dead tumor cells, has been extensively studied in recent years. This DNA is easily accessible from liquid bio-psies such as blood or other patient's bodily fluids.

Purpose: This article summarizes current scientific knowledge on cfDNA and ctDNA, particularly in the context of malignant lymphoma, and foreshadows its potential future uses.

Conclusion: Detection and analysis of cfDNA represents a new approach that can lead to future improvements in all phases of lymphoma treatment from diagnostics to minimal residual disease monitoring.

Background: The evaluation of treatment outcomes and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC) treated by enzalutamide or abiraterone after previous docetaxel.

Patients and methods: We analyzed 66 patients with mCRPC treated by enzalutamide (55 patients) or abiraterone (11 patients) after previous therapy with docetaxel. The median follow-up was 31.2 months. Enzalutamide and abiraterone were administered in daily doses of 160 mg and 1,000 mg per day, respectively. The progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis. The prognostic influence of the factors on OS was evaluated by regression analysis.

Results: The progression was observed in 55 (83%) patients, and mPFS was 12.1 (95% CI 7.7-16.4) months. In total, 43 patients died, and he median OS was 21.9 (95% CI 12.2-31.7) months. In the regression analysis, we observed statistical favorable influence of the following factors on OS: PSA decrease ≥ 50%, in patients with early decrease of prostatic specific antigen (PSA) ≥ 50% in 3 months after initiation of enzalutamide or abiraterone treatment, in patients with visceral metastatic sites, in patients treated with only one regimen of previous chemotherapy and in those without anemia. We observed the toxicity grades 3-4 in 45.5% and 36.3% patients treated with enzalutamide and abiraterone, respectively.

Conclusion: Our analysis demonstrated efficacy and good tolerance in patients with mCRPC treated with enzalutamide and abiraterone after previous docetaxel therapy.

Background: An integrated analysis of phase III trials in patients with advanced solid tumors demonstrated superiority of denosumab over zoledronic acid in preventing skeletal-related events. A drug's clinical efficacy, however, depends on regular and continued administration (persistence); persistence in Slovak real-life is yet undetermined for denosumab in the oncology indication.

Patients and methods: This was a single-arm, prospective, observational, non-interventional study in patients with bone metastases from solid tumors treated with denosumab every 4 weeks in real-world clinical practice in 5 European countries. The results of the 54 patients from Slovakia are presented here. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively.

Results: Previous skeletal-related events were found in 5.6% of patients. 84.8% were persistent over 24 weeks and 61.4 % over 48 weeks. The median (95% confidence interval (CI)) time to non-persistence was 306.5 days (Q1 = 151.0; Q3 = 315.0). The most frequent reason for non-persistence was delayed administration of denosumab. There was a trend towards weaker analgesics over time, with > 70% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the whole study. Adjudicated osteonecrosis of the jaw was not documented in any Slovak patient.

Conclusion: Most patients received denosumab regularly once every 4 weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions was in line with expectations from previous studies, osteonecrosis of the jaw did not occur in any of the patients involved in the study.

Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma in the Western world. It is an indolent disease in most patients, but about 20% of patients experience an early relapse after initial treatment, which is associated with shorter overall survival. A histological transformation into an aggressive lymphoma, most frequently diffuse large-cell B-lymphoma, represents another prognostically unfavorable event in the course of the disease. Thanks to recent genomic studies and mouse models, we are able to better understand the molecular nature of the FL onset and evolution of "aggressive" subclones of cells. Recently, deregulation of several molecular pathways associated with the histological transformation has also been described.

Purpose: This review summarizes the complex molecular mechanisms responsible for FL onset, progression, aggressiveness, and transformation. We believe that the observations in FL have some general implications for understanding the mechanisms leading to the evolution of cancer "aggressiveness," such as divergent evolution, intraclonal variability and tumor plasticity.

Background: Pediatric-inspired protocols with prospective monitoring of minimal residual disease (MRD) are considered the standard of intensive treatment for adults with acute lymphoblastic leukemia (ALL). They have been used in the Czech Republic since 2007.

Patients and methods: Two hundred and ninety-seven patients aged 18-65 years were treated at five hematology centers between 2007-2020 according to the GMALL 07/2003 protocol. This is a retrospective analysis of their treatment outcomes.

Results: In the Ph-negative cohort, 189 (93.1%) patients achieved complete remission, 5 (2.4%) patients were refractory, and early mortality was 3.0%. Seventy (34.5%) patients experienced relapse in a median of 10.6 months. Overall survival (OS) at 3 and 5 years was 63.5% and 55.9%, disease-free survival (DFS) at 3 and 5 years was 54.5% and 49.7%, respectively. Young adults under 35 years of age (P = 0.015), patients without initial CNS infiltration (P = 0.016), with MRD negativity before consolidation treatment (P < 0.001), transplanted in the 1st complete remission (P < 0.001), and subjects treated after 2012 (P = 0.05) had significantly better overall survival. In a multivariate analysis, MRD at week 11 was the only independent factor affecting OS (HR 3.06; P = 0.006). For DFS, baseline CNS infiltration (HR 2.08; P = 0.038) and MRD at week 11 (HR 2.15; P = 0.020) were significant. In the Ph-positive cohort, 84 (89.4%) patients achieved complete remission, 1 (1.0%) patient was refractory, early mortality was 4.3%. Twenty-six (27.7%) patients relapsed in a median of 8.6 months. Survival at 3 and 5 years was 57.2% and 52.4% for OS and 50.2% and 44.9% for DFS, respectively. Transplanted patients and patients diagnosed after 2012 had statistically better overall survival (P < 0.001).

Conclusion: The introduction of pediatric-inspired protocols with treatment intensification according to MRD levels resulted in a significant improvement in the survival outcomes of adult patients with ALL.