Jana Skřičková, David Petr
David Vrána, Nikol Rušarová, Marek Szkorupa
Daniel Krejčí, Jana Krejčí, Norbert Pauk
Marie Drösslerová, Libor Havel
Josef Dvořák, Igor Richter, Jan Prokš, Aneta Rozsypalová, Jana Grimová
Radek Lakomý, Alexandr Poprach
Surgery is mostly used to treat non-small cell lung cancer in early stage I and II. Surgery can be used in stage IIIA but also together with chemoradiotherapy. Surgery is not normally used to treat small cell cancer; small cell lung cancer is treated only with T1—2(3) NO M0 attributes. The aim of surgery treatment is complete removal of tumorous cells (RO) with surrounding lymphatic tissue.
In the treatment of lung cancer, the basic modality is radiotherapy, which has proven therapeutic benefits in both radical and palliative indications in up to 76% of all patients. In the Czech Republic, the proportion of patients with bronchogenic carcinoma receiving radiotherapy has not exceeded 25% in the long term. In the case of clinically inoperable non-small-cell lung cancer (NSCLC) in stage I, the method of choice is stereotactic radiotherapy, which allows local control in more than 80% after three years. Postoperative radiotherapy is suitable in the case of involvement of mediastinal nodes. In locally advanced inoperable NSCLC, the standard of treatment is concomitant chemoradiotherapy given concomitantly with chemotherapy based on a double combination of cytostatics containing a platinum derivative. A flat dose escalation above 60 Gy / 6 weeks has not been shown to be useful, as it increases toxicity with a higher risk of death. Technical innovations such as beam intensity modulated radiotherapy, image-guided radiotherapy or time-tracking of breathing movements bring improvements in treatment outcomes. The clear benefit of proton beam therapy has not been demonstrated. In small cell carcinoma, concomitant chemoradiotherapy is the most effective in the stage of limited disease, starting at the latest from the third cycle of chemotherapy. Radiotherapy is also recommended in the stage of extensive disease as a consolidation treatment after chemotherapy with a very good response. For the treatment of small cell carcinomas, preventive brain irradiation is recommended as a standard, although recent studies have reported close and frequent MRI monitoring and early treatment in asymptomatic as an alternative. In NSCLC, preventive radiation reduces the proportion of patients with the development of brain metastases from 30% to 8%, but this has not been shown to prolong survival.
In recent years, non-small cell lung carcinoma (NSCLC) treatment has developed rapidly. Biological treatment preparations have improved survival in NSCLC, particularly in non-operable locally advanced and metastatic NSCLC. Substances that target the processes inside tumor cells are particularly useful in adenocarcinomas. At the time of diagnosis, it is necessary to determine the morphological diagnosis as accurately as possible and, if indicated, to perform genetic testing. In our paper we give an overview of the development and possibilities of biological treatment.
Immunotherapy, a new modality in the treatment of non-small cell lung cancer, provides patients with advanced disease with the possibility of effective treatment with less toxicity. Immune checkpoints treatment utilizes highly selective humanized monoclonal antibodies in order to reactivate anti-tumor response. This treatment improves overall survival, extends the spectrum of treatment options, and is less toxic compared to chemotherapy. Immune-mediated adverse reactions can lead to a variety of clinical conditions and can include any organ in the body. While the indication of immunotherapy is likely to expand in the future, further knowledge is needed to determine the optimal combination with chemotherapy, radiotherapy and other anticancer drugs, as well as finding optimal biomarkers to predict the therapeutic effect and toxicity of immunotherapy.
Malignant pleural mesothelioma represents a disease with poor prognosis. There is currently no accepted general standard of care however as available published data indicate the multimodality approach combining chemotherapy (neoadjuvant or adjuvant, based on cisplatin/carboplatin and pemetrexed), surgery and eventually perioperative pleural chemotherapy lavage seem to bring the most benefit. This approach is suitable for only limited group of patients in a good performance status, without any distant metastatic disease and without clinically significant comorbidities. Further research is therefore needed to define the optimal treatment algorithm for malignant pleural mesothelioma.
Epidermal growth factor receptor (EGFR) mutations are found in 10-14 % lung cancer patients in Central Europe. Therapeutic standard for these patients are EGFR-tyrosinkinase inhibitors (TKI). Screening for these mutations became a diagnostic standard in adenocarcinoma histology. Majority of these mutations are sensitizing mutations (Del 19, exon 21 point mutations). Main resistance mechanism after prior EGFR tyrosinkinase inhibitors therapy is exon 20 mutation T790M. Osimertinib is third generation EGFR tyrosinkinase inhibitors that selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations.
Worldwide, lung cancer is one of the most common oncological disease. Targeted analysis of the mutation status in non-small cell lung carcinoma detects 10-15 % of patients with a mutated epidermal growth factor receptor gene, whose presence is significant prognostically and therapeutically.1 Diagnosis is based on molecular-genetic methods.2 Depending on the patient's performance status and type of mutation, the patient is indicated for therapy with tyrosine kinase inhibitors, which in this group of patients promise a good response to treatment with a favorable safety profile.13
Targeted therapy enables patients with non-small cell lung cancer (NSCLC) with driver mutations prolongation of overall survival and improvement quality of life compared to chemotherapy. Crizotinib is one of biological drugs. It is a tyrosine kinase inhibitor targeting ALK (anaplastic lymphoma kinase) gene rearrangement. Crizotinib is indicated for the first-line treatment of adults with ALK positive advanced NSCLC and for the treatment of adults with previously treated ALK positive advanced NSCLC. It is also indicated for the treatment of ROS1 positive advanced NSCLC. Crizotinib has a good safety profile and tolerability. Our article describes a clinical case report of ALK positive advanced NSCLC patient with rare choroidal metastasis that responds to crizotinib. Vision of our patient improved with crizotinib. The quality of life was definitely better.
Pembrolizumab is a humanized monoclonal antibody against programmed cell death 1 receptors (PD-1) (an IgG4/K isotype with a stabilizing sequence change in the Fc region) produced by recombinant DNA technology in Chinese hamster ovary cells.
Triple negative breast cancer constitutes a heterogeneous group of diseases with limited systemic treatment options. A new perspective treatment modality is immunotherapy with check point inhibitors. The phase III randomized control trial IMpassion130 demonstrated a significantly prolonged progression free survival and overall survival in first line treatment of metastatic or locally advanced inoperable triple negative breast cancer with atezolizumab and nab-paclitaxel, exclusively in patients with programmed death-ligand 1 (PD-L1) ≥ 1 % expression on tumor infiltrating immune cells.
Surgical excision is the curative treatment in most cases of early cutaneous melanoma. Prognosis of patients with high-risk primary melanoma or with nodal involvement remains poor. Impact of adjuvant interferon alfa on overall survival is limited. The recently published results from the randomized phase III trials with immunotherapy - anti-PD-1 antibodies (nivolumab, pembrolizumab) and with targeted therapy (dabrafenib + trametinib) are very promising. These new adjuvant treatment modalities are able significantly reduce the rate of disease recurrence. However, there are many unresolved questions. Especially, we do not know what is better in BRAF mutant melanoma, if targeted therapy or modern immunotherapy? We need reliable biomarkers of tumor progression and prognosis for better selection really high-risk patients and the optimal type of adjuvant treatment. The side effect profile of treatment and patient preference will play an important role in decision-making process.
Breast cancer is the most common malignity in female population. Over the past years, incidence hasn't risen as well as prognosis has improved. Although the newly diagnosed women under 40 makes just small part of all cases, with higher age of reproduction start, after-treatment pregnancy has been increasingly frequent question. Available data shows that pregnancy after treatment is safe regardless of type and stage, if started after treatment, respectively after breast cancer diagnose. Pregnancy was observed in patients treated at our center in years 2003-2016. It was recorded 44 pregnancies at 29 women in total. It was born 38 healthy children; 1 dead and 5 gravidities were early terminated. Only one patient died of disease progression, which occurred during pregnancy, other patients are in long term disease remission. Average observation time is 9,5 years. Our observation results confirm after treatment pregnancy safety, according to published data.
Gastric neuroendocrine neoplasms are rare lesions consisting of a heterogenous group of neoplasms. The majority of them arise from ECL (enterochromaffin-like) cells - neuroendocrine cells of gastric mucosa, which produce histamin and have the impact on the regulation of gastric secretion. This is why we can call them “ECLomas”. Their incidence is increasing, due to the widespread use of upper digestive endoscopy and the technical refinement of endoscopists. Gastric neuroendocrine neoplasms comprise tumor types of varying pathogenesis, histomorphologic characteristic, biological behavior and prognosis. They can present with clinical symptoms, or can be asymptomatic, carcinoid syndrome is extremely rare. The correct management of patients with gastric neuroendocrine neoplasms can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient.
Cancer treatment may be accompanied by a number of side effects. We always try to educate our patients, they are equipped with a telephone emergency number and often also with rescue medication, which they can use in case of problems (antiemetics, antidiarrheals, analgesics, etc.). Nevertheless, there may be situations where patients go with their problems primarily to a general practitioner (they do not use the recommended medication, or the recommended medication is not enough, the patient did not pick up the drugs in the pharmacy and so on). Good cooperation between a general practitioner and an oncologist is therefore very important. The most common side effects of oncological treatment including immunotherapy and their management in general practitioner will be presented in the article.