Stanislav Hloušek, Milada Zemanová, David Feltl
Jana Krejčí, Daniel Krejčí, Petr Opálka
Jana Katolická, Jiří Vaníček
Radmila Lemstrová, Martina Spisarová
Zuzana Šporiková, Vladimíra Koudeláková, Marián Hajdúch
Libor Staněk, Kristýna Glendová, Robert Gürlich, František Mateička
Igor Sirák, Petra Sýkorová, Jakub Grepl, Petr Paluska, Šárka Kollárová, Iva Dostálová, Martin Kopeček, Martina Šůnová, Monika Sedláčková, Linda Kašaová, Miroslav Hodek, Milan Vošmik
Sabina Svobodová, Adam Peštál, Igor Suškevič
Robert Novák, Jana Katolická, Vladimír Červeňák
The gold standard is lobectomy and systematic mediastinal lymphadenectomy. In high-risk patients, sublobar resections may be considered in very selected cases. VATS (video-assisted minithoracothomy, minithoracotomy) resection becomes the method of choice for faster recovery of patients, lower morbidity and comparable oncological effectiveness compared to open chest surgery. Centralization to high-volume specialized pneumo-oncosurgical centers is key for good results.
Modern pulmonary diagnostic and therapeutic bronchology is a dynamically developing discipline, which has long been focused not only on endobronchial problems but also on diagnosis and treatment of parenchymal pathologies of mediastinum and pleural cavity. We remain in the standard division of the endoscopic method as determined, even though it is increasingly perceived as being overwhelmed by the potential of hybrid and combined procedures.
Adjuvant systemic therapy after radical resection of non‑small cell lung cancer – reality and new possibilities
Adjuvant chemotherapy (AC) after radical resection is a standard treating method of non-small cell lung cancer (NSCLC) in stage IB (in tumors of 4 cm in diameter), II and IIIA. The recommendation is based on the results of extensive meta-analyzes, which confirmed the reduction in the relative risk of death and an absolute improvement in the 5-year survival rate from 4% to 5%. Due to relatively low profits and side effects, AC use is limited in practice. Combination of vinorelbine with cisplatin is preferred, but carboplatin is used as well, particularly in patients with older age, worse performance status and co-morbidities. Current efforts aim to improve efficacy and patient selection. Prognostic and predictive biomarkers are sought to allow the personalization of adjuvant chemotherapy. In patients with NSCLC after radical surgery, other systemic treatment options are verified. Biologically targeted treatment has not yet been unambiguously put into common practice although two studies have shown improved survival with long-term TK inhibitors in the epidermal growth factor receptor (EGFR) mutation tumors. There are several extensive Phase 3 studies with immunotherapy in patients with different PDL-1 expressions. Their results are expected with great hope.
In the treatment of pulmonary cancer, radiotherapy is a basic method that has demonstrated therapeutic benefit in both radical and palliative indications in up to 76% of all patients. In the Czech Republic, the proportion of patients with bronchogenic carcinoma treated with radiotherapy does not exceed 25%. In the case of clinically inoperable non-small cell lung cancer (NSCLC) in stage I, stereotactical radiotherapy is the method of choice which allows local control of the disease up to 90% of the patients after three years while it's efficiency is comparable to the surgery with better tolerance. Postoperative radiotherapy is appropriate for the affected mediastinal lymph nodes. In locally advanced inoperable NSCLC, the standard of concomitant chemoradiotherapy is co-administered with chemotherapy based on the two platinum-containing cytostatics. No flat-rate escalation over 60 Gy/6 weeks for increased toxicity with higher risk of death has been demonstrated. Flat-rate escalation over 60 Gy/6 weeks has not been proven useful as it increases the toxicity and the risk of death. Technical innovations, such as beam-modulated radiotherapy, image-based radiotherapy, or breathing movement monitoring over time, improve treatment outcomes. Technical innovations, such as beam-modulated radiotherapy, image-based radiotherapy, or breathing movement monitoring over time, improve treatment outcomes. In small-cell carcinoma, at the stage of limited disease, the most effective is concomitant chemoradiotherapy, starting at the latest from the third cycle of chemotherapy, at a dose of 66 Gy/33 fractions or twice daily for 3 weeks to a dose of 45 Gy. Radiotherapy is also recommended at the extensive disease stage as a consolidation treatment after chemotherapy with a very good response. In the treatment of small cell carcinomas, preventive brain irradiation is recommended as standard, although recent studies, as an alternative, include careful and frequent magnetic resonance imaging (MR) and early treatment in an asymptomatic stage. In NSCLC, preventive irradiation reduces the proportion of patients with brain metastasis from 30% to 8%, but survival prolongation has not been demonstrated.
The author presents a case of a 70-year-old man, a current smoker on the treatment for COPD and internal comorbidities, who underwent the diagnostic procedures for a tumor located in the apex of the right upper pulmonary lobe. After the complete pulmonary function tests the right upper lobectomy was indicated and subsequently performed. Due to the clinical stage IIB the adjuvant chemotherapy was administered. The discussion engages in the pulmonary function tests before the lung resection.
Stereotactic radiotherapy as an alternative to surgical treatment at the early stage of non‑small cell lung cancer
Case presents a patient with non-small cell lung cancer at clinical stage IA3, who refused surgical removal of the tumor. Instead of surgery, the patient was offered a variant with stereotactic radiotherapy that the patient agreed to and underwent without complications. Partial remission was observed in subsequent CT scans. One year after the therapy the patient is without signs of progression or generalization. The case therefore presents an alternative to standard surgical treatment for patients for whom, for various reasons, this modality is not indicated or preferred.
Lung cancer is one of the most common and most serious diseases. At present, we have different treatment approaches for non-small cell lung cancer not only according to histology but also on the basis of molecular genetic properties. Different treatment strategies exist according to molecularly defined markers in non-small-cell lung cancer. Molecular testing for at least epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) should be performed in all patients before therapy. Crizotinib is a tyrosine kinase inhibitor targeting ALK translocation. Based on Profile 1007 and Profile 1014 trial, it has become the basis of treatment for patients with ALK translocation. Our case report is a demonstration of the good performance of crizotinib in the second line of treatment of patients with lung adenocarcinoma.
Metastatic urothelial carcinoma is a chemotherapy sensitive disease and platinum-based chemotherapy is the standard primary treatment. Vinflunine is a third-generation antimicrotubuline agent of the vinca alkaloid class. In a randomized study a prolongation of overall survival was shown in eligible patients. The data from European studies represents the excellent experience with vinflunine in patients in daily clinical practice.
Cabozantinib is a novel multitargeted tyrosine kinase inhibitor that improved progression-free survival and overall survival in patients with advanced renal cell carcinoma after one or more prior vascular endothelial growth factor receptor targeted therapies. The safety profile of cabozantinib is acceptable.
Combination of BRAF and MEK inhibitors in the treatment of advanced malignant melanoma harbouring BRAF V600 mutation
Immunotherapy and targeted therapy have radically changed prognosis of patients with advanced malignant melanoma. Nowadays up to 40 % of patients reach long term remission of disease. Around 50 % of malignant melanomas harbor BRAF V600 mutation. Combination of BRAF and MEK inhibitors in the treatment of BRAF V600 mutated melanomas has led to increased efficacy with acceptable toxicity of the treatment. Unfortunately, the secondary resistance develops to combination therapy too. New strategies to overcome the secondary resistance are subject of many clinical trials as well as appropriate sequence of treatment of BRAF V600 mutated melanoma. The results of ongoing clinical trials will hopefully lead to further optimizing of the treatment. This review summarizes the combination of vemurafenib and cobimetinib in the treatment of advanced BRAF V600 mutated malignant melanoma.
Current oncology is mainly focused towards the search of novel prognostic and predictive biomarkers, new therapeutics and therapeutic strategies leading to the development of personalized medicine. Current diagnostics of breast cancer uses the estrogen, progesterone and HER2 expression for prediction of endocrine and anti-HER2 therapy response and prognosis determining. Recently, BRCA1 and BRCA2 mutation testing for prediction of response to PARP inhibitors was introduced into clinical practice. In last decade, a number of biomarkers have been identified, however, they must be clinically validated by independent prospective study. The properly validated biomarkers have huge significance in current personalized oncology.
Human papillomavirus (HPV) is a double stranded DNA virus with a tropism to skin epithelia and mucosa of genital tract or upper airways. It is transmitted mainly by sexual intercourse and enters the body through microscopic injuries. Based on their ability to induce cancer these were further divided into low-risk and high-risk subgroups. Low-risk subgroup is responsible for the presence of viral verrucas. The high-risk subgroup is related to malignant anogenital dysplasias and also dysplasias in areas of head and neck. It is speculated that based on the change in profile of patients with HNSCC (head and neck squamous cell carcinoma) papilloma viruses increase the risk of cancer development and are causally related to the development of HNSCC independent of the two main carcinogens - tabaco and alcohol. Interestingly HPV positive HNSCC patients have dissimilar molecular characteristics and are related to better prognosis, therapy response and higher overall survival. They may profit from anti-EGFR therapy by cetuximab, but without defined predictors, such as those known in CRC patients.
Radiotherapy and particulary brachytherapy have been major treatment modalities for cervical cancer for over 100 years. Most of this time the brachytherapy treatment planning was based on radiographs and reference point dosimetry. Due to research of European Society for Radiotherapy and Oncology (GEC-ESTRO) a 3D brachytherapy planning, based on the magnetic resonance imaging with adaptation of the treatment to actual tumor regression in time (4D), has become a standard of care in the last decade. University hospital in Hradec Kralove is the first center in the Czech Republic to implement the adaptive brachytherapy planning of cervical carcinoma based solely on the magnetic resonance imaging for each fraction.
Pheochromocytomas are rare tumors. Bilateral adrenal medullary pheochromocytomas are components of MEN- Ila and MEN Ilb (multiple endocrine neoplasia). Patient 55 years old with inoperable pheochromocytoma, with liver and abdomen cavity metastases in the time of diagnosis had high levels of adrenalin, noradrenalin and dopamin. Patient was treated by TACE, lanreotide and target therapy. The patient lives 5 years after the diagnosis of disease dissemination and 18 years after the first manifestation, with very good effect and quality of life. The case demonstrates the good effect of hormonal and anti-cancer treatment.
Differentiated carcinomas represent 90% of all thyroid malignancies. Median survival in radiofrequency (RAF) carcinomas (10-20% of all tumors) is 2.5-3.5 years. New knowledge in the field of molecular genetics has been the basis for the development of new systemic drug therapies. The multikinase inhibitor lenvatinib is authorized for the treatment of RAF differentiated thyroid carcinoma on the basis of a randomized, placebo-controlled clinical study achieving 18.3 months of progression-free with levantinib versus 3.6 months compared to the placebo. The safety profile is comparable to other tyrosine kinase inhibitors and side effects associated with treatment with lentavinib are manageable. The indication limitation is for the patients not treated with another tyrosine kinase inhibitor in ECOG 0-1 state. In conclusion, we add a personal case report (patient's testimony) with a long-term effect of administering lenvatinib.
Ovarian cancer is one of the most aggressive oncological diseases and it has the highest mortality amongst gynecological malignancies. It is the fifth most common cause of death in women with malignant neoplasms all over the world. A wide variety of histological units is present in ovarian cancer and the most common type is a serosal ovarian cancer that belongs to a group called epithelial tumours.1 In 2016, 998 new patients were diagnosed with ovarian cancer and in the same year 628 women died from the ovarian cancer in the Czech Republic.2 The statistics show that this type of neoplasm is not very common, however, the mortality rates are one of the highest for this type of cancer. 75 % of diagnosed patients are already in advanced or metastatic stages. The main reasons are rapid tumour growth and late onset of symptoms. On top of that we are still very behind with getting tested and diagnosed in time. Despite aggressive treatment the percentage to survive at least five years is 23-35 % with Stage III, 10 % with Stage IV.3 The standard treatment of ovarian cancer is the combination of surgical treatment and chemotherapy. With surgery the tumours should drastically shrink and then systemic therapy should be in place. The ovarian cancer is generally highly chemo sensitive tumor and platinum derivative preparations are primarily used in the treatment. Primarily, for relapse we use systemic treatment, surgical treatment is used very rarely. Depending on the time when the primary or prior treatment ended we can distinguish platinum-resistant disease (relapse within six months of termination of the platinum-based treatment) and platinum-sensitive disease (relapse after more than six months after termination of the platinum-based treatment). Based on these two types of diseases we then choose other products for systemic therapy of the disease. Most common chemotherapeutic agents are carboplatin or cisplatin, paclitaxel, docetaxel, gemcitabine or pegylated liposomal doxorubicin. Medicine with a non-cytotoxic mechanism used in palliative systemic therapy can be for example bevacizumab or olaparib.
The targeted therapy of the patient with pulmonary metastases of colorectal cancer in a the sequence of bevacizumab‑panitumumab‑regorafenib
In the course of the disease more than half of the patients with colorectal cancer creates metastases to distant organs. The liver is the first site of metastases in 80 %, followed by the lungs. The basis of the system of treatment of metastatic colorectal cancer is chemotherapy. This targeted therapy increases its beneficence. An important therapeutic modality is surgical resection of metastases, which has the potential to improve overall survival, which today exceeds 30 months. The case report demonstrates that suitably elected treatment can achieve a multimodal overall survival of the patient and a good quality of life even in the metastatic stage of oncological disease approximately in years. It shows the current options for the targeted treatment of metastatic colorectal cancer. It confirms the long-term efficacy of the targeted treatment, maintaining good effect while applying a sequence of VEGF antibodies against anti EGFR inhibitor.
The case of long‑term response with good quality of life at the patient with cholangiocellular carcinoma
Cholangiocarcinoma is a disease with poor prognosis with 5-year survival 5-15%. In our case report we are presenting the case of long term response of pacient with intrahepatic cholangicarcinoma, after complete resection, with repeated recurrencies, after repeated surgical inetrventions and administrations of chemotherapy.