Magyar onkologia最新文献

Since the III. Breast Cancer Consensus Conference, a number of new evidence based on clinical trial results have been published which justified updating the 2016 recommendation. In addition to classical prognostic factors, some multigenic tests, which we have incorporated into the recommendation, will play an important role in therapeutic decision-making. The professional guide primarily reflects the resolutions and recommendations of the current ESMO, NCCN, ABC4, as well as the St. Gallen Consensus Conference. From a didactic point of view, the text follows first the line of early and then locally advanced breast cancer, locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to therapeutic options.

The surgical treatment is still the most effective method in curing of early breast cancer. Breast preservation and the application of oncoplastic principles became generally accepted, the sentinel lymph node biopsy in the surgical treatment of the axilla is primary, and the indication for axillary block dissection (ABD) is narrowing further. The neoadjuvant oncological treatment that is applied more and more widely presented surgery with new challenges. Hereunder we summarise our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

Breast radiologists and nuclear medicine specialists have updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference. They suggest to adopt this actual protocol for the screening, diagnostics and treatment of breast tumors from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the followup. Suggestions for improvement of the current Hungarian practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The guidance has been in agreement with the related medical disciplines.

The radiotherapy (RT) expert panel revised and updated the RT guidelines accepted in 2016 at the 3rd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional WBI. Following mastectomy RT significantly decreases the risk of LR and improves overall survival of patients having 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by BCS WBI is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

Follow-up includes the permanent contact with and health education of the patient, the surveillance and control of the adverse effects of surgery, oncological therapies or radiotherapy, the screening of metachronous cancers, and the comprehensive (physical, psychological and social) rehabilitation of the patient which may be enhanced by healthy life-style. The early detection and curative management if necessary, of local/regional tumor relapse is still a priority but the routine screening of distant metastases by means of imaging studies or tumor marker tests is not justified. Supportive therapy means to endocrine therapy, available social support in Hungary, and the key issues and managing tools of physical and psychooncological care are provided. Individual solution of special issues (breast cancer risk/genetic mutation, pregnancy) may be served by widening options. Ideally, follow-up is practised by a cooperative team of oncologists, surgeons, breast radiologists, social workers, physiotherapists, psychiatrists. The follow-up approach should be comprehensive and holistic.

There have been some relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2016 recommendations made during the 3rd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 4th Hungarian Breast Cancer Consensus Conference. The recommendations cover non-operative, intraoperative and postoperative diagnostics, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future. The most important changes include the integration of the TNM 8th edition, the WHO classification of breast tumors 5th edition, the ASCO/CAP HER2 assessment guidelines from 2018, and the Yokohama terminology for cytology reporting; a more detailed text on tumor-infiltrating lymphocytes and size determination after neoadjuvant therapy and a broader discussion of molecular tests.

KRAS mutations are the most common gain-of-function alterations in lung adenocarcinoma (LADC) in the western countries. Although the different mutations of the KRAS gene have been identified decades ago, the development of drugs targeting the KRAS protein directly have not been successful due to the lack of small molecule binding sites and the extremely high affinity to cellular GTP. Indirect strategies to inhibit KRAS (e.g. inhibitors of farnesyltransferase, prenylation, synthetic lethal partners and KRAS downstream signaling) have so far also failed. In recent times, however several compounds have been developed that target subtype- specific KRAS mutations. Covalent KRAS G12C-specific inhibitors showed the most promising preclinical results. Below, we summarize the predictive and prognostic value of KRAS mutations in LADC as well as the current targeting strategies.

Molecular classification of lung cancer developed in the past decades to the level where even the rare genetic alterations are included. Unfortunately, adenocarcinoma benefited from this development almost exclusively. Furthermore, the tumor-agnostic novel therapy indications influence the molecular diagnostics of lung cancer including microsatellite status, tumor mutation burden or NTRK fusion gene determinations. On the other hand, the still low resection rate of lung cancer and limited availability of tumor tissue for diagnosis opened the way of routine use of liquid biopsy technologies. The routine use of target therapies triggered the development of various genetic resistance mechanisms, the monitoring of which gradually became a standard of monitoring of the disease. Beside the "targeted" diagnostics, multigene panel testing or whole exome sequencing are more frequent, resulting in a more complex genetic picture of lung cancer. This requires the categorization of genetic alterations into predictive levels for standard, investigational or hypothetic target therapies in the molecular pathology reports.

More than 6 million mutations of more than 600 cancer genes can occur in over 200 tumor types according to the COSMIC (Catalogue of Somatic Mutations in Cancer) database. The theoretical combination of all "driver" alterations and tumor types adds up to an enormous number. Therefore, there is a legitimate need to use the same targeted therapy in the presence of its target and mechanism of action in multiple tumor types. The first tissue-agnostic drugs that are registered solely based on molecular biomarkers are the NTRK inhibitors (larotrectinib and entrectinib) and the PD-1 inhibitor pembrolizumab in microsatellite instable (MSI) and tumor mutation burden (TMB) high tumors. These targets are also present in lung cancer, and we have clinical proof of the activity of treatments. In addition, the molecular targets of many targeted therapies registered in other tumor types occur in lung cancer for target-based tissue-agnostic therapy planning in lung cancer.

The unprecedented development of prostate cancer therapy is a challenge for the proper sequential use of modern medicines. Patients' life expectancies improve when we use treatment lines, one after the other. There is no evidence- based guideline regarding the optimal sequence, but a number of data are available to help the physician selecting the best individualized therapeutic option. The basic treatment for advanced prostate cancer is still androgenic deprivation (ADT), to which we can add additional therapeutic agents. New types of hormonal (androgen receptor targeted, ARTA) agents are being used in an increasingly early line. Chemotherapy (CT) is the first choice in case of metastatic, hormone-sensitive disease especially in high volume cases that are causing symptoms or visceral crisis. CT is otherwise applied after ARTA. We have little but encouraging data about the early, sequential use of ARTAs with different mechanisms of action. In later lines, cross-resistance may develop between ARTA treatments, in which cases CT is the right decision. In this paper, we summarize the results of clinical trials that may help in therapeutic decision making, maximizing the benefits for patients.