Klinicka Onkologie最新文献

Background: Cervical cancer has shown declining incidence and mortality in recent years, yet it remains a serious societal problem. This is mainly due to its prevalence in younger age groups and the relatively difficult treatment of advanced stages. Treatment of the early stages is predominantly in the hands of gynecologists, while modern radiation therapy combined with systemic therapy is now the standard treatment for advanced stages. More controversial is the indication and position of neoadjuvant systemic therapy before surgery or radiotherapy. In addition to chemotherapy, the role of immunotherapy in metastatic disease is increasing. The addition of immunotherapy to radiation therapy in locally advanced disease also improves oncological outcomes.

Aim: This article summarizes current primarily nonsurgical therapies and outlines directions in the treatment of cervical cancer.

Background: Gastrointestinal stromal tumors (GISTs) are rare tumors of the digestive tract that have seen significant advances in diagnosis and treatment in recent years. A key breakthrough was the identification of c-KIT and PDGFRA gene mutations, which enabled the introduction of targeted therapies. The cornerstone of the treatment for localized disease is radical (R0) surgical resection, with adjuvant imatinib recommended for patients at high risk of recurrence. In advanced or metastatic disease, standard care involves sequential treatment with tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib. A major advance is represented by ripretinib, which effectively inhibits a broad spectrum of KIT and PDGFRA mutations and has been shown to prolong survival in patients with advanced GIST refractory to current options of systemic therapy. The expanding range of targeted therapies, such as avapritinib for the PDGFRA D842V mutation, underscores the importance of molecular profiling in guiding optimal treatment strategies.

Aim: This review aims to summarize current knowledge on the diagnosis and treatment of GIST, with a focus on the role of molecular-genetic profiling, the therapeutic value of individual tyrosine kinase inhibitors, and emerging options for advanced disease, with particular emphasis on ripretinib.

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder characterized by an extreme lifetime risk of multiple and early-onset tumors, driven by inherited pathogenic variants in the TP53 gene. While somatic mutations in TP53 are among the most frequent genetic alterations in cancer, germline mutations remain rare. Although LFS has long been recognized as a prototypical cancer predisposition syndrome, recent advances have significantly reshaped its diagnostic criteria and deepened our understanding of its associated cancer risks.

Objective: The review illustrates the evolving diagnostic landscape of LFS and the updated indication criteria for germline TP53 testing, which have broadened the definition of the syndrome into the more inclusive entity of heritable TP53-related cancer predisposition syndrome (hTP53rc). The adoption of NGS has streamlined molecular diagnostics in hereditary cancer syndromes. Germline analysis of TP53 has become standard practice in hereditary cancer predisposition testing, even if a proband does not exhibit a LFS phenotype. However, the accurate identification of germline pathogenic TP53 variants remains challenging, particularly due to confounding factors, such as mosaicism or clonal hematopoiesis of indeterminate potential. Confirmatory testing using an independent tissue sample, along with estimation of allelic fraction is necessary to distinguish true germline variants. Another major hurdle is the assessment of the pathogenicity of rare germline TP53 variants, which requires a thorough genotype-phenotype correlation analyses. Recently, gene-specific American College of Medical Genetics and Genomics / Association for Molecular Pathology criteria have been introduced to support the classification of germline TP53 variants. Importantly, only carriers of a clearly established germline pathogenic variant should be considered for inclusion in an intensive clinical surveillance and prevention program.

Conclusion: The present work underscores a paradigm shift in the understanding of one of the most significant cancer predisposition syndromes and aims to stimulate further discussion on the organization of care for high-risk carriers of pathogenic TP53 variants in the Czech Republic.

Background: Recently, there has been interest in the CT imaging characteristics of lung cancer positive for mesenchymal-epithelial transition (MET) exon14 skipping mutation. Herein, we present a patient with MET exon 14 skipping gene-positive lung adenocarcinoma associated with multiple ground-glass opacities (GGOs) in both lungs and metachronous contralateral lung adenocarcinoma.

Case: A 67-year-old man was referred to our hospital due to abnormal finding on chest radiograph. A chest CT on admission revealed a mass in the right lung. A chest CT scan showed a mass in the middle lobe of the right lung, and numerous GGO nodules of various sizes in both lungs. The mass was resected and it was diagnosed as a MET exon 14 skipping gene-positive invasive adenocarcinoma. A GGO nodule resected at the same time was pathologically diagnosed as atypical adenomatous hyperplasia (AAH). A GGO nodule in the left lung that was present at the initial consultation grew in size on a CT scan performed 1 year and 4 months after the right lung resection, and was therefore resected. The nodule was pathologically diagnosed as a MET exon 14 skipping gene-negative invasive adenocarcinoma. Genetic testing for an AAH adjacent to the second adenocarcinoma was negative for the MET exon 14 skipping gene.

Conclusion: The clinical course of this patient was interesting clinical information in terms of providing insight into the morphology, imaging findings, and origin of MET exon 14 skipping gene-positive adenocarcinoma.

Background: This study aims to evaluate the relationship between sentinel lymph node positivity and risk factors associated with cutaneous melanoma, as well as the epidemiological data of patients diagnosed with this condition in the Blumenau-SC region.

Material and methods: This is a cross-sectional study analyzing medical records of patients diagnosed with melanoma who underwent sentinel lymph node biopsy at a nuclear medicine service in Blumenau, Santa Catarina. The variables analyzed included Breslow classification, Clark classification, regression, ulceration, histological subtype, age, and sex. Patients were divided into two groups: those with a positive diagnosis and those with a negative diagnosis.

Results: The variables with the highest statistical significance were: histological subtype, with nodular melanomas associated with positivity (P < 0.001); ulceration, which was more prevalent in the positive group (P = 0.0018); Breslow classification, which showed a significantly higher mean in the positive group (P = 0.0002, Mann-Whitney test); and Clark level, which was significant in patients with higher classifications. Other variables analyzed did not show statistical significance.

Study limitations: The mitotic index was not analyzed as a variable; this study was based on the 7th edition of the American Joint Committee on Cancer (AJCC) cancer staging manual.

Conclusion: This study presented results consistent with current literature, confirming the predictive values of sentinel lymph node positivity, aiding in better patient selection for this invasive procedure, and avoiding unnecessary analyses that may lead to irreversible adverse effects.

Background: The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient's biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS.

Material and methods: To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library.

Results: Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P < 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P < 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P < 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease.

Conclusion: The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.

Background: The patient's quality of life is an integral part of the evaluation of anticancer treatment. We can meet its evaluation mainly within the framework of clinical studies and research projects, but it is increasingly included in routine clinical practice as well. In radiotherapy, this indicator needs to be evaluated especially with the advent of new fractionation regimes, which are supposed to ensure better clinical results, but also the same or better quality of life for patients compared to another fractionation scheme. There are several ways to measurably evaluate the quality of life. Questionnaires filled in by patients are most often used, so this is a subjective approach. It is essential to choose the right methodology, especially the type and form of questionnaires with regard to the specific situation (diagnosis, treatment, etc.).

Aim: In this educational review article, quality of life and its role in the treatment of a patient with radiotherapy are defined. Next, selected methods of quality of life assessment in radiotherapy are described in detail. Emphasis is placed especially on available questionnaire surveys, generic or specific. Among the most commonly used quality of life questionnaires are those from the EORTC group, FACIT questionnaires and the EQ-5D, SF-36, WHOQOL-100 and WHOQOL-BREF questionnaires. The general EORTC QLQ-C30 questionnaire, which is also often used in radiotherapy, is used to demonstrate the assessment on one specific example of a questionnaire completed by a patient.

Conclusion: The quality of life of an oncology patient ranks among the most important evaluations of care outcomes (patient reported outcomes measures), and data collection for its evaluation should be part of routine clinical practice in radiation oncology as well, especially when introducing a new fractionation regimen. The purpose of this educational review article is to point out the various possibilities for evaluating the quality of life, different types of generic and specific questionnaires, and also to emphasize certain recommendations and procedures necessary for quality evaluation of questionnaires.

Background: Polyclonal hypergammaglobulinemia has a variety of causes, which we outline in the text. Regularly, very high concentrations of polyclonal immunoglobulins are observed in IgG4-related disease, Sjögren's syndrome, and in the idiopathic multicentric Castleman disease.

Observation: We describe a patient who had induration of the salivary glands and an immunoglobulin IgG level of 42 g/l. Over the course of 3 months from the first contact, there was a significant overall deterioration: skin rash presumably due to vasculitis, impaired kidney function with pathological proteinuria, exophthalmus, and heart failure. Increased concentration of subclass immunoglobulin IgG4, along with histological assessment of the excised salivary gland, led to the diagnosis of a IgG4 related disease.

Results: The treatment was started with prednisone, which very soon led to the manifestation of diabetes mellitus, and therefore we requested approval for rituximab from the healthcare payer. We chose a regimen in which the effect of rituximab is further potentiated by adding cyclophosphamide and dexamethasone. The patient received 6 cycles consisting of rituximab 800 mg on the 1st day of the cycle. Additionally, dexamethasone 20 mg and cyclophosphamide 600 mg were administered on the 1st and 15th days of the 28-day cycle. The treatment led to a complete remission, with duration for 24 months at the time of evaluation. The patient is scheduled for maintenance treatment with rituximab 1,000 mg infused at 6-month intervals, but we extend these intervals if the disease markers (the concentration of IgG4 subclass immunoglobulin and the number of circulating plasmablasts in peripheral blood) are completely normal.

Conclusion: The Mikulicz phenotype of the IgG4-related disease is characterized not only by the involvement of exocrine glands but also by damage to other organs (kidneys, cardiovascular system and skin). This disease tends to progress rapidly if not timely halted with effective treatment, in our case a combination of rituximab with a low dose of cyclophosphamide. Cyclophosphamide has the potential in this disease not only to potentiate glucocorticoid therapy, but our experience confirms published data that it enhances the effect of rituximab and presumably also prolongs the duration of the treatment response.

Background: Solitary hepatocellular carcinoma (HCC) with a diameter of 3-5 cm represents a challenging clinical entity, especially for non-surgical candidates due to comorbidities.

Case: A 74-year-old man with previous history of renal cell carcinoma presented with a new incidental solitary 5 cm liver lesion on MRI. Due to his age and a high risk for post-surgical complications, after multidisciplinary tumor board review the treatment plan consisted of percutaneous thermal segmentectomy using balloon-occluded microwave ablation (b-MWA) followed by balloon-occluded transarterial chemoembolization (b-TACE) with complete tumor necrosis, as evident in subsequent follow-up imaging. This case demonstrates that b-MWA plus b-TACE could be a safe and effective combined therapy for unresectable large HCC lesions, even for those exceeding 3 cm in size.

Conclusion: Although the presented case is anecdotal and naturally without comparisons or control, it highlights the potential value of percutaneous thermal segmentectomy with a single session combined b-MWA followed by b-TACE for the treatment of large unresectable solitary HCC lesions.