Current status of durvalumab in the lung cancer treatment

05/2021 Doc. MUDr. David Vrána, Ph.D.
Lung cancer represents one of the most frequent type of cancer. They can be classified as non-small cell lung cancer and small cell lung cancer. The treatment strategy of these tumors unfortunately didn't change significantly over the last couple years until the immunotherapy and tyrosine kinase inhibitors were launched into daily clinical practice. Immunotherapy, more specifically checkpoint inhibitors has quickly established their role in the treatment of several tumor types and nowadays has confirmed their effectivity in the first line of the palliative treatment of the non-small cell and small cell lung cancer including the maintenance therapy of the non-small cell lung cancer after radical chemoradiotherapy. Durvalumab is the monoclonal antibody against programmed cell death-ligand 1 (PD-L1), which blocks the interaction of the ligand PD-L1 and programmed cell death 1 receptor (PD-1) / CD80 which leads the significant increase in the immune response against cancer. At the same time this influencing of the immunity has brought the new adverse events which are different from the adverse events of the chemotherapy or tyrosine kinase inhibitors.

Osimertinib in adjuvant treatment EGFR+ non‑small cell lung cancer – ADAURA trial

05/2021 MUDr. Ondřej Bílek
Approximately one-quarter of patients with non-small cell lung cancer are diagnosed with early or locally advanced stage of the disease suitable for surgery. There is a high risk of disease recurrence after adjuvant chemotherapy. The ADAURA trial demonstrated a significant benefit of adjuvant treatment with osimertinib in patients with non-small cell lung cancer with evidence of aberration of EGFR del19 or L858R in exon 21.

STRN‑ALK fusion, rare variant of ALK gene – case report

05/2021 MUDr. Jaromír Roubec, Ph.D.; MUDr. Jaroslav Krátký
In connection with their own case report, the authors discuss the issue of rare mutations in the gene for anaplastic lymphoma kinase (ALK), known mechanisms of increased tumorigenesis of such mutated non-small cell lung cancer tumors and the possibilities of their therapeutic management using tyrosine kinase inhibitors. Literature sources and documented cases of a rare STRN-ALK fusion mutation are presented.

Atezolizumab in the treatment of lung cancer

05/2021 MUDr. Leona Koubková
Immuno-oncotherapy is already an integral part of lung cancer treatment. Especially in the first line treatment of non-small cell lung cancer (NSCLC) either in monotherapy of tumors with high expression of programmed cell death protein ligand 1 (PD-L1) or in combination with other treatment modalities leads to prolongation of overall survival and survival without progress. Atezolizumab, a monoclonal antibody against PD-L1, has been approved by the European Medicines Agency based on a number of studies to treat firstand higher-line NSCLC and as a first-line checkpoint inhibitor for first-line extensive small cell lung cancer.

Actual immunotherapeutic options in pneumooncology

05/2021 MUDr. Daniel Krejčí; doc. MUDr. Norbert Pauk, Ph.D.
Lung carcinoma remains aggressive tumour with bad prognosis. In the last decades there was a significant improvement in lung cancer treatment especially with contribution of immunotherapy and targeted therapy. The use of check point inhibitors brought better overall survival and quality of life in lung cancer patients. Following text summarizes actual immunotherapeutic options in lung cancer and other thoracic malignancies.

Biologically targeted treatment in non‑small cell lung cancer or „do we always have mutations and PD-L1 examined?“ – case report

05/2021 MUDr. Gabriela Krákorová, Ph.D.
Metastatic or locally advanced non-small cell lung cancer (NSCLC) generally has a very poor prognosis. Five-year survival in stage IV is in the order of percentage units (less than 5%). Lung tumors with control mutations present are „different" tumors, with different behavior and prognosis. Treatment should always be initiated with knowledge of the mutation status and expression of programmed cell death-ligand 1 (PD-L1). PD-L1 expression should be reflexively determined in all NSCLC at the time of diagnosis by a pathologist and EGFR, ALK, ROS mutations reflexively in non-squamous NSCLC. The article presents a case report of a patient, where the omission of this examination may lead to the wrong choice of treatment scheme, but at least to a delay in the start of treatment. The article further discusses the possibilities of biologically targeted treatment for individual types of control mutations in lung cancer - EFGR, ALK, ROS, BRAF, KRAS, etc.

Status of radiotherapy and concomitant chemoradiotherapy in locally advanced non‑small cell lung cancer and small cell lung cancer

05/2021 MUDr. Tereza Kohlová; doc. MUDr. Renata Soumarová, Ph.D.; Ing. Anna Negri; Ing. Šárka Šípová
Radiotherapy is the basic treatment modality in lung cancer across all its stages. There is a therapeutic benefit in settings up to 77 per cent, but the worldwide use is lower, in the Czech Republic about 25 percent. The advanced radiotherapeutic techniques, such as IMRT (intensity modulated radiotherapy) and IGRT with monitoring of respiratory motion (image guided radiotherapy), enable to reduce a dose to the organs at risk (heart, contralateral lung), the risk of pneumonitis and they prolong the survival.

Avelumab and its therapeutic use in uro‑oncology

05/2021 MUDr. Jindřich Kopecký, Ph.D.
Immunotherapy has become an integral part of cancer therapy over the last decade. Treatment of uro-oncological malignancies is no exception. Gradually, nivolumab, pembrolizumab, and ipilimumab have become cornerstones for renal and bladder cancer therapy. Avelumab is becoming another monoclonal antibody that is effective in these cancers. And although it could be said to be another of the molecules. This treatment brings not only the possibility of a wider choice of effective therapy but also, for example, in the case of urothelial carcinoma, a new way of use.

Alpelisib – the first PI3K inhibitor in the treatment of hormone‑positive, HER2‑negative breast cancer

05/2021 MUDr. Stanislav Hloušek
Despite all the progress of recent years, hormone therapy is still the main treatment modality in most patients with breast cancer. However, even for this treatment, resistance and disease progression may develop over time then it is necessary to find therapy for the second and higher lines of treatment. A suitable candidate for this situation appears to be alpelisib - an α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor which, in combination with fulvestrant, has been shown to be effective in patients with advanced hormone-dependent, human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer where PI3K catalytic subunit alpha (PIK3CA) mutations have been identified, after disease progression to hormonal therapy, even if cyclin dependent kinase 4/6 (CDK4/6) inhibitors have been used. This efficacy was documented in the SOLAR-1 study in patients after hormonal treatment failure compared to placebo and in the BYLieve study, which enrolled patients after previous progression to CDK4/6 inhibitors.

New treatment options of transitional cell carcinoma of the urinary bladder in the era of immunotherapy

05/2021 MUDr. Tomáš Blažek; doc. MUDr. Renata Soumarová, Ph.D., MBA
The treatment of transitional cell carcinoma of the urinary bladder has been changed and evolved over the last decade. New findings in the field of immuno-oncology research largely contribute to treatment improvements. Conventional treatment modalities, i.e. surgical treatment, radiotherapy and systemic chemotherapy are expanded in the light of emerging immunotherapy options. Historically, one of the first immunotherapeutic agents was the attenuated Bacillus Calmette-Guérin (BCG) vaccine. It was used for the treatment of superficial, non-invasive transitional cell carcinomas of the bladder. Since that, the study of immune mechanisms and interactions in the tumor microenvironment, supported with the efficacy of the BCG vaccine, contributed to the development of further improvements in immunotherapy. In the modern era of immunotherapy, new active molecules, i.e. checkpoint inhibitors, are used. The use of these active molecules, targeting surface receptors located on the tumor cells and immune system of the patient, offer new perspectives in the systemic treatment of metastatic or locally advanced transitional cell carcinoma of the urinary bladder. Specific aspects of immunotherapy, particularly the effectiveness, tolerance and toxicity profile, which have an important impact on the quality of life of patients, make immunotherapy a new, alternative modality in addition to conventional systemic chemotherapy. The purpose of this article is to provide an overview of the current possibilities of systemic therapy for bladder cancer using immunotherapy and checkpoint inhibitors.

Systemic treatment of hepatocellular carcinoma

05/2021 MUDr. Beatrix Bencsiková, Ph.D.
Hepatocellular carcinoma (HCC) is a heterogeneous disease with an increasing incidence. Despite advances in systemic treatment, patients' prognosis remains poor. The outcome of treatment is affected by the extent of the disease, comorbidities of the patient, performance status, functional status of the liver parenchyma. Tyrosine kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib), a monoclonal antibody against the vascular endothelial growth factor receptor (ramucirumab), improve overall patient survival. After more than ten years, the programmed cell death ligand inhibitor 1 atezolizumab in combination with bevacizumab statistically significantly prolonged the survival of patients with unresectable HCC. The aim of the article is to present the possibilities of systemic treatment of HCC in the first and second line of treatment.

BRCA‑positive ovarian cancer – case report

05/2021 MUDr. Klaudia Regináčová; doc. MUDr. Martina Kubecová, Ph.D.
In our case report we present a patient with BRCA-positive ovarian cancer, who was diagnosed with stage IV and underwent treatment modalities which were accessible. In the case report, we wanted to emphasize the importance of a multidisciplinary team, the need for genetic testing in treatment decisions, as well as the impact of antiangiogenic and targeted treatment on the patienťs survival in a good quality of life.

Coincidence of oropharyngeal carcinoma and systemic progressive sclerosis in a 47‑year‑old patient – case report

05/2021 MUDr. Kateřina Licková; MUDr. Aleš Čoček, Ph.D.
Systemic progressive sclerosis is an autoimmune disease of unclear etiology characterized by vasculopathy and fibrosis. The incidence of malignancies in patients with this serious disease is higher than in the general population. The cause of this predisposition is not yet clearly defined. In our case we present a patient with systemic progressive sclerosis who was diagnosed with oropharyngeal carcinoma. The aim of this work is to draw attention to the complications in differential diagnosis and therapy in concurrent systemic autoimmune and cancer.

Medullary thyroid carcinoma – case reports

05/2021 MUDr. Andrea Jurečková
Two case reports of patients with metastatic medullary thyroid carcinoma treated with tyrosine kinase inhibitors as a 1st line treatment are presented. The effectiveness of the treatment is compared - long-term treatment response in patient with early detected metastatic disease versus quick progression in patient with late diagnosis of advanced carcinoma and large proportion of metastatic lesions.

Treatment of lung metastases in prostate cancer – case reports

05/2021 MUDr. Eva Kindlová
Prostate cancer is one of the most common cancers in men. Approximately 20 % of diagnosed patients had already developed metastases, in others the tumor may generalize after the locoregional treatment. The most frequent are bone and lymph nodes metastases, less frequented sites of metastases are lungs, liver, and other organs. The ways of treatment depend on whether the tumor is metastatic hormone-naive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC). Both local and systemic therapies are possible for treating lung metastases. Modalities of local therapy are surgical therapy and radiotherapy; hormone therapy, chemotherapy and ARTA therapy can be administered as systemic therapy. It is necessary to choose the optimal sequence of modalities and even use several lines of therapy to reach the best response. That can result in significant improvement of patienťs life expectancy and his quality of life as well.