Magyar onkologia最新文献

The molecular pathological examination of solid tumors is essential not only for supporting histological diagnosis but also for detecting hereditary variations and predictive biomarkers. Analyzing predictive markers is fundamental to personalized cancer therapy, directly affecting patient care through pathological testing. These analyses employ both traditional immunohistochemical staining methods and molecular genetic techniques. In both approaches, preanalytics is of critical importance, necessitating the adoption of standardized and reproducible processes. Molecular diagnostics in colorectal cancer focuses on detecting activating mutations in the MAPK pathway (KRAS, NRAS, BRAF), as well as evaluating microsatellite instability and HER2 amplification. Immunohistochemical methods can effectively identify biomarkers for gastric cancers, including the novel claudin18.2. The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

Aim: In our institute, we have been testing EGFR T790M resistance mutations since 2019, which is the most common resistance mutation that develops during first-line, second- line EGFR TKI treatment of EGFR mutant lung adenocarcinomas. The importance of this study is that the identification of this mutation will allow the use of an effective third-generation TKI. In this article, we report on studies from January 2022 to August 2024, compared with our results from the 2019-2021 period.

Methods: 380, predominantly blood samples from 222 patients were tested during the present period using Super- ARMS EGFR Mutation Detection Kit (AmoyDx).

Results: EGFR mutations were identified in 57% of all samples in the primary tumours, with a 38.3% frequency of T790M mutation.

Conclusions: Our results were similar to the previous period. The number of rebiopsies was essentially unchanged compared to the 2019-2021 period, which may be the main reason why we were able to identify the mutation in a lower percentage compared to the T790M hit rate described in the literature.

The implementation of targeted therapies in oncology has brought significant improvement in the treatment of many solid tumours. At the same time, pathological and molecular pathological diagnostics became more important. Today, there are hardly any solid tumours that do not require predictive biomarker testing. In recent years, a number of new targeted therapies have emerged for gynaecological tumours, prostate and breast cancer. In this article, we summarise the molecular pathology tests required in these tumours based on current clinical and pathological guidelines.

RASopathies are congenital diseases that manifest in childhood with symptoms and potential complications, typically associated with an elevated tumour predisposition risk. The heterogeneous symptoms involve mostly central nervous, cardiovascular, musculoskeletal systems and skin, and modified growth pattern. From molecular perspective, the function of a key protein involved in Ras signalling is impaired, leading to disrupted regulation of cell growth and division. It is crucial to uncover genetic history, analyse tumour and cardiac involvement pattern along four generation pedigree and depict minor anomaly pattern. Upon clinical suspicion a stepwise approach to molecular testing is recommended to confirm or rule out the specific RASopathy. Post-test genetic counselling should address potential complications, developmental and follow-up strategies in line with current guidelines. Cascade pedigree segregation analysis according to the inheritance pattern should be offered to family planning parents and potentially affected family members. In case of certain specific organ involvement or complications, targeted therapeutics are available, highlighting the importance of early diagnosis.

This review presents the latest molecular genetic diagnostic and clinical aspects related to clonal hematopoiesis of indeterminate potential (CHIP). CHIP belongs to the continuously expanding group of pre-cancerous conditions, increasingly recognized in routine patient care due to the development of molecular diagnostic tools and the increase in life expectancy. The incidence of CHIP mutations increases with age (1-2% in individuals aged 50 years, 15-45% in those aged 80 years). According to international studies, 5-8% of examinations performed on solid tumors may contain erroneous results due to the presence of leukocytes. This rate increases to 10-15% in case of liquid biopsy samples. To avoid misleading diagnostic results, it is recommended to perform comparative analysis of samples from different tissue origins, blood/tumor sample pairs. The authors illustrate CHIP-related alterations affecting targeted therapies for solid tumors (e.g. KRAS, ATM, IDH1, TP53). The impact of CHIP on the detection of germline genetic alterations is also discussed.

In recent years, there have been remarkable improvements in the treatment of hematological malignancies with the introduction of novel therapeutic modalities. The advent of these therapies has made it feasible to significantly and permanently decrease (possibly eradicate) tumor cells in the body. Evaluating the effectiveness of these treatments required the development of a new diagnostic method. Currently, the most appropriate approach for assessing the objective response is through the measurement of "measurable residual disease" (MRD). MRD refers to the presence of malignant cells in a patient's body after receiving treatment, even in the absence of apparent signs or symptoms. Several techniques can be employed to detect MRD, including multiparametric flow cytometry, RQ-PCR as well as more recent approaches including digital PCR or next generation sequencing. This review offers an in-depth overview of the different techniques used to estimate measurable residual disease and their current applications in hematological malignancies.

In malignant hematological diseases, clonal genetic alterations, such as chromosomal aberrations and gene mutations, are responsible for the uncontrolled division of abnormal hemopoietic cells. The detection of clonal variants has not only diagnostic, but also prognostic and therapeutic significance. They enable risk-based differentiated treatment of patients and the use of targeted (genotype-specific) therapies. Chromosomal abnormalities can be identified with cytogenomic testing (karyotyping, fluorescent in situ hybridization - FISH, microarray). In chronic myeloid leukemia, myelodysplastic neoplasia and acute leukemias, chromosome analysis is a mandatory test at the time of diagnosis. In some lymphoid malignancies (chronic lymphocytic leukemia, multiple myeloma), instead of karyotyping, submicroscopic abnormalities and translocations are detected by FISH method. Despite the rapid spread of high-sensitivity new-generation sequencing techniques, cytogenetic studies are still essential in the routine diagnosis of malignant hematological diseases.

Aim: This study aims to evaluate the diagnostic challenges and molecular aspects of pediatric gliomas, among the most common brain tumors in children, focusing on improving early detection and personalized treatment strategies.

Methods: We conducted a comprehensive review of recent literature, examining current diagnostic techniques, including imaging and histopathological analysis, alongside molecular profiling methods such as next-generation sequencing (NGS) and methylation profiling.

Results: The findings highlight significant diagnostic challenges due to the heterogeneity of pediatric gliomas. Molecular profiling has proven essential in identifying key genetic alterations, such as those in the H3F3A and MAPK pathway genes, offering insights into tumor behavior and therapeutic targets.

Conclusions: Early and accurate diagnosis of pediatric gliomas is hampered by their molecular diversity. Integrating molecular diagnostics with traditional methods is crucial for enhancing diagnostic accuracy and guiding personalized treatment approaches.

Treatment of locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT), including induction or consolidation chemotherapy. Introduction of immunotherapy has brought success in several solid tumors and hematological diseases. In colorectal tumors, it was only introduced later. A general predictive biomarker is the deficient mismach repair (dMMR) status and consequent microsatellite instability (MSI-H). In these tumors, immune checkpoint inhibitor (ICI) therapy is the first-choice therapy in metastatic colorectal cancer. ICIs have been used in earlier, non-metastatic stages in several studies, with breakthrough results in the microsatellite-unstable patient group and recently in combination with neoadjuvant CRT in rectal tumor patients with pMMR/MSI-L status. In our report we focused on the recent immune checkpoint inhibitor treatment of metastatic and locally advanced colorectal cancer, as a monotherapy, or combined with chemo- or radiotherapy. We summarize the studies with the most promising results.

Our objective was to present the perioperative and oncological results of robot-assisted surgery performed in our department. In our publication, we retrospectively reviewed the data of 658 robot-assisted procedures performed between 01/02/2022 and 31/03/2024. The average operative time for radical prostatectomy with bilateral lymph node block dissection was 229 minutes, mean blood loss was 305 ml. Without lymphadenectomy, mean blood loss was 233 ml, operative time was 185 minutes. Biochemical relapse- free rate was 81.6% one year after the procedures. 165 patients underwent robot-assisted partial nephrectomy, and 48 patients underwent radical nephrectomy. We performed the first robot-assisted cystectomy with intracorporeal "neobladder" technique in Hungary. In terms of urinary diversion, we performed orthotopic bladder formation in 10 cases, Bricker bladder formation in 20 cases, and uretherocutaneostomia in 4 cases. We also performed the first robot- assisted retroperitoneal lymphadenectomy in the country. As a conclusion, using robot-assisted technology, the full spectrum of radical uro-oncological surgical procedures can be safely performed in a minimally invasive manner. Our experience and results are encouraging so far, validating the increasing domestic distribution of robotic surgery.