Klinicka Onkologie最新文献

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.

Background: Idiopathic multicentric Castleman disease (iMCD) is characterized by constitutional symptoms, enlarged lymph nodes and laboratory test abnormalities, which are primarily related to the overproduction of interleukin-6 (IL-6). This form (iMCD) was treated earlier with cytostatics used for lymphoma, later with bio-logic therapy as rituximab, immunodulatory drugs and proteasome inhibitors, and in the last years with an anti-IL-6 antibody, siltuximab. Siltuximab is a human-mouse chimeric immunoglobulin G1k monoclonal antibody against human IL-6 approved in the European Union for the treatment of iMCD. In view of the limited treatment options for iMCD, this case report aimed to evaluate the efficacy and safety of siltuximab in the management of this condition.

Case: We describe a young woman with iMCD diagnosed at the age of 25 years. For first line treatment, rituximab and dexamethasone were used without any cytostatic because the patient wished to give birth to a healthy child in the future. However, the response after this first line therapy was short. In addition, after 3 years from the start of rituximab + dexamethasone therapy, it was necessary to administer treatment for the relapse of iMCD. We decided for siltuximab in this young woman, still aged < 30 years, and started administration of siltuximab in 3-week intervals.

Results: After administration of first two infusions of siltuximab, all inflammatory markers returned to normal value. Moreover, serum hemoglobin and albumin levels as well as C-reactive protein normalized after the first two administrations of siltuximab. The clinical response continue, siltuximab is still administered in 3-week intervals. PET/CT with fluorodeoxyglucose confirmed a very good anatomic and metabolic response to the treatment. Siltuximab demonstrated a favorable safety profile, and the prolonged treatment was well tolerated.

Conclusion: This result is encouraging and demonstrates the potential of siltuximab as treatment of CD. As earlier published, this case confirms that significantly elevated inflammatory markers in a patient with CD predict a good response to siltuximab.

Background: Progress in cancer dia-gnostic and treatment increases the probability of survival and survival time in cancer patients. Current research focuses on the quality of life of cancer survivors and the late effects of treatment, which can take the form of cognitive failures in daily life. The aim of the presented research was to examine the relationships between subjectively-reported cognitive failures and selected socio-demographic, clinical, and psychological characteristics (age, hormonal treatment, depression, anxiety, fatigue, sleep satisfaction).

Patients and methods: The research sample consisted of 102 cancer survivors aged 25-79 years and a mean time since the end of the last treatment was 17.4 months (standard deviation = 15.4). The largest part of the sample consisted of breast cancer survivors (62.4%). The level of cognitive errors and failures was measured by the Cognitive Failures Questionnaire. The PHQ-9 Patient Health Questionnaire, the GAD-7 General Anxiety Disorder Scale, and the WHOQOL-BREF Quality of Life Questionnaire were used to measure depression, anxiety, and selected aspects of quality of life.

Results: An increased level of cognitive failures in daily life was found in approximately one-third of cancer survivors. The overall cognitive failures score is strongly related to the level of depression and anxiety. Decreasing levels of energy and sleep satisfaction are associated with increasing cognitive failures in everyday life. The age and hormonal therapy do not significantly differentiate the level of cognitive failures. In the regression model, which explained 34.4% of the variance of subjectively-reported cognitive functioning, depression was the only significant predictor.

Conclusion: The study results mention relationship between subjective evaluation of cognitive functioning and emotional experience in cancer survivors. The administration of self-reported methods for measuring cognitive failures can be helpful in clinical practice in identifying psychological distress.

Background: Breast cancer is a complex, multifactorial disease influenced by many genetic factors. Besides the relatively rare pathogenic variants in high or moderate penetrant cancer predisposition genes, breast cancer risk is modified by numerous low risk alleles considered to be polygenic genetic factors. While the risks associated with individual polygenic loci are negligible, its cumulative effect can reach clinically significant values and it can be expressed as a polygenic risk score (PRS). PRS is recently considered to be a possible tool improving assessment of absolute and cumulative risks at the individual level.

Purpose: Several single nucleotide polymorphism sets for PRS assessment have recently been developed and prepared for their implementation into clinical practice. The following text aims to explain the fundamental principles of the PRS assessment and its interpretation as a candidate prediction tool. The use of the PRS should always depend on genetic analysis of pathogenic variants in cancer predisposition genes including its current limitations.

Background: Hypoplastic myelodysplastic neoplasm (MDS-h) is a rare hematopoietic disorder characterized by peripheral cytopenia, hypoplasia (cellularity ≤ 25%) and dysplastic changes in the bone marrow. Compared to normo- /hypercellular MDS, in addition to hypocellularity, MDS-h patients have more profound neutropenia and thrombocytopenia, a lower percentage of blasts, and less frequent abnormal karyotype. It is difficult to distinguish MDS-h from aplastic anemia in differential diagnosis. Abnormal karyotype is found in 15-50% of MDS-h patients and the most common chromosomal aberrations include -5/del (5q), -7/del (7q), +8, 17pLOH, del (20q), UPD at 4q, 11q, 13q, and 14q. Approximately 35% of MDS-h patients harbour somatic mutations that are most often detected in PIGA, TET2, DNMT3A, RUNX1, NPM1, ASXL1, STAG2, and APC genes. An autoimmune destruction of hematopoietic stem cells (HSCs) or hematopoietic progenitor cells (HPCs) mediated by abnormally activated T cells plays a key role in the pathophysiology of MDS-h. Expanded T cells overproduce proinflammatory cytokines (IFN- g and TNF-a), which inhibit proliferation and induce apoptosis of HSC/HPCs. The antigens that trigger the immune response are not known, but potential candidates have been suggested such as WT1 protein and HLA class I molecules. MDS-h does not represent a phenotypically homogeneous subtype of MDS, but rather it is a mixed entity comprising both patients showing features similar to myelodysplastic neoplasm and patients with features of non-malignant bone marrow failure. Determining the prevailing phenotype in MDS-h is important for choosing the optimal treatment and prognosis prediction.

Purpose: The aim of this article is to point out an interesting hypoplastic MDS, the diagnosis of which is difficult, and to provide an overview of its main clinical-pathological features, genetic background, and mechanisms of aberrant immune response.

Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear.

Material and methods: OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by the next generation sequencing (NGS), and OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa-circ-0006203 - hsa-circ-0004872, the primer design and RT-PCR were performed. The expression levels were detected by RT-qPCR.

Results: The NGS results demonstrated that circRNAs were abundantly expressed in OSCC, and two circRNAs were significantly differentially expressed. hsa-circ-0006203 - hsa-circ-0004872 were significantly downregulated in OSCC tissue samples and was statistically correlated with pathological differentiation.

Conclusion: In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, it was our team who firstly explore the regulatory role of the hsa-circ-0006203 - hsa-circ-0004872 network in OSCC. The results indicated that hsa-circ-0006203 - hsa-circ-0004872 may be a potential biomarker for OSCC.