Selected articles
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Long‑term surviving patient with EGFR mutation – deletion on exon 19 and acquired resistant mutation T790 – case report
06/2020 MUDr. Gabriela Krákorová, Ph.D.; doc. MUDr. Jan Baxa, Ph.D.; prof. MUDr. Miloš Pešek, CSc.
Metastatic lung cancer has a very poor prognosis, with a 5-year survival of about 5%. Pulmonary malignancies with a control mutation for which biologically targeted drugs are available have a better prognosis, as shown by a case report of a patient with a sensitive control EGFR mutation. Tumor biopsy and peripheral blood sampling, liquid biopsy, were performed repeatedly during treatment to detect the acquired T790 resistance mutation, among other things. The patient survives with metastatic lung adenocarcinoma for eight years, still with a good quality of life. The case report shows that due to a suitably selected treatment sequence according to the presumed or known genetic profile of the tumor, even metastatic lung cancer can change from such a serious disease to a chronic one.
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Metastatic lung cancer has a very poor prognosis, with a 5-year survival of about 5%. Pulmonary malignancies with a control mutation for which biologically targeted drugs are available have a better prognosis, as shown by a case report of a patient with a sensitive control EGFR mutation. Tumor biopsy and peripheral blood sampling, liquid biopsy, were performed repeatedly during treatment to detect the acquired T790 resistance mutation, among other things. The patient survives with metastatic lung adenocarcinoma for eight years, still with a good quality of life. The case report shows that due to a suitably selected treatment sequence according to the presumed or known genetic profile of the tumor, even metastatic lung cancer can change from such a serious disease to a chronic one.
Lung carcinoma – imaging on the molecular level
05/2020 Prof. MUDr. Jiří Ferda, Ph.D., MUDr. Eva Ferdová, doc. MUDr. Jan Baxa, Ph.D., prof. MUDr. Miloš Pešek, CSc., MUDr. Petr Mukenšnabl, Ph.D., doc. MUDr. Hynek Mírka, Ph.D.
Molecular imaging in lung carcinoma are being the basic diagnostic approaches in the confirmation of the tumorous origin of the disease, but also in staging and restaging of the disease. Positron emission tomography / computed tomography (PET/CT) with the application of 18F-fluorodeoxyglucose is the most frequent molecular imaging in lung tumors, it is used as the fundament of the clinical stage of the disease before start of the treatment. Positron emission tomography / magnetic resonance imaging (PET/MRI) enables to complete the imaging with the full valid brain magnetic resonance imaging during the own procedure, the main disadvantage of PET/MRI is the prolonged scanning, making time unacceptable for those patients, who are heavier clinical state. The alternative way of the pharmacokinetics evaluation could be the analysis of iodine content within tissues using dynamic perfusion computed tomography (CT) or dual-energy CT. The use of other radiopharmaceuticals like 18F-ftuorthymidine in tissue proliferation or 68Ga-DOTA derivate in the assessment of somatostatin receptor density could provide the supplementary information about tumor biology.
ENTIRE ARTICLE
Molecular imaging in lung carcinoma are being the basic diagnostic approaches in the confirmation of the tumorous origin of the disease, but also in staging and restaging of the disease. Positron emission tomography / computed tomography (PET/CT) with the application of 18F-fluorodeoxyglucose is the most frequent molecular imaging in lung tumors, it is used as the fundament of the clinical stage of the disease before start of the treatment. Positron emission tomography / magnetic resonance imaging (PET/MRI) enables to complete the imaging with the full valid brain magnetic resonance imaging during the own procedure, the main disadvantage of PET/MRI is the prolonged scanning, making time unacceptable for those patients, who are heavier clinical state. The alternative way of the pharmacokinetics evaluation could be the analysis of iodine content within tissues using dynamic perfusion computed tomography (CT) or dual-energy CT. The use of other radiopharmaceuticals like 18F-ftuorthymidine in tissue proliferation or 68Ga-DOTA derivate in the assessment of somatostatin receptor density could provide the supplementary information about tumor biology.
Atypical response to anti‑PD‑1 therapy followed by long‑term survival in non‑small cell lung cancer – case reports
02/2020 MUDr. Gabriela Krákorová, Ph.D.; MUDr. Marek Šťastný, Ph.D.; MUDr. Hana Steinbergerová; MUDr. Jana Důrová; prof. MUDr. Miloš Pešek, CSc.; doc. MUDr. Jan Baxa, Ph.D.
Metastatic non-small cell lung cancer has poor prognosis. In the absence of driving mutations (EGFR, ALK, ROS, BRAF) or high expression of programmed death-ligand 1 (PD-L1), chemotherapy or its combination with bevacizumab is the initial treatment option with respect to reimbursement conditions in the Czech Republic. The second line possibility is the use of immunotherapy with inhibitors of protein 1 of programmed cell death (anti-programmed death-1, anti-PD-1) or inhibitors its ligand, anti-PD-LI. The authors present two case reports of patients, who had an atypical response following immunotherapy. This was the persistent effect of immunotherapy, despite the progression on this treatment. The first patient had no need for another active oncology treatment for further 12 months after immunotherapy and the malignancy had not been significantly progressing. The second patient developed a significant response to chemotherapy following anti-PD-1 immunotherapy. This phenomenon, in the literature referred not quite correctly to as chemosensitization, is repetitively described. Next the authors also consider the possibilities of treatment of the next line after immunotherapy failure.
ENTIRE ARTICLE
Metastatic non-small cell lung cancer has poor prognosis. In the absence of driving mutations (EGFR, ALK, ROS, BRAF) or high expression of programmed death-ligand 1 (PD-L1), chemotherapy or its combination with bevacizumab is the initial treatment option with respect to reimbursement conditions in the Czech Republic. The second line possibility is the use of immunotherapy with inhibitors of protein 1 of programmed cell death (anti-programmed death-1, anti-PD-1) or inhibitors its ligand, anti-PD-LI. The authors present two case reports of patients, who had an atypical response following immunotherapy. This was the persistent effect of immunotherapy, despite the progression on this treatment. The first patient had no need for another active oncology treatment for further 12 months after immunotherapy and the malignancy had not been significantly progressing. The second patient developed a significant response to chemotherapy following anti-PD-1 immunotherapy. This phenomenon, in the literature referred not quite correctly to as chemosensitization, is repetitively described. Next the authors also consider the possibilities of treatment of the next line after immunotherapy failure.
Immunotherapy and radiotherapy in locally advanced (metastatic) non‑small cell lung cancer
01/2020 Special Edition - MUDr. Gabriela Krákorová, Ph.D.; MUDr. Hana Steinbergerová; prof. MUDr. Miloš Pešek, CSc.; prof. MUDr. Jindřich Fínek, Ph.D., MHA; MUDr. Tomáš Svoboda, Ph.D.
Non-small cell lung cancer even today is a big socioeconomic problem for beeing diagnosed in an advanced or metastatic stage in majority of tumors when our treatment methods available at that time unfortunately are not associated with satisfactory results except few patients with tumors carrying specific mutations. Radiochemotherapy remains the basic standard regimen while adding induction or maintenance cytotoxic treatment did not count for any other benefit. However, modern immunotherapy by PD-1 and PD-L1 inhibitors brings a huge hope today. Mainly it's combination with radiation therapy sensibilizing to a better immunotherapy effect could become a standard part in majority of treatment guidelines. In this context, hypofractionated radiation regimens with limited target volumes seem to be preferred to normofractionation and larger fields. The role of abscopal effect remains still uncertain.
ENTIRE ARTICLE
Non-small cell lung cancer even today is a big socioeconomic problem for beeing diagnosed in an advanced or metastatic stage in majority of tumors when our treatment methods available at that time unfortunately are not associated with satisfactory results except few patients with tumors carrying specific mutations. Radiochemotherapy remains the basic standard regimen while adding induction or maintenance cytotoxic treatment did not count for any other benefit. However, modern immunotherapy by PD-1 and PD-L1 inhibitors brings a huge hope today. Mainly it's combination with radiation therapy sensibilizing to a better immunotherapy effect could become a standard part in majority of treatment guidelines. In this context, hypofractionated radiation regimens with limited target volumes seem to be preferred to normofractionation and larger fields. The role of abscopal effect remains still uncertain.
Non‑small cell lung cancer with ALK and ROS1 genes rearregement
05/2018 Prof. MUDr. Miloš Pešek, CSc.
In a review author present the state - of the art of diagnostics and therapy of advanced non-small cell lung cancer with ALK and ROS1 genes rearrangements. Diagnostic processes are realized in specialized pathologic departments with the help of histology, imunohistochemistry and fluorescent in situ hybridization. Patients suffering by either with ALK positive NSCLC, or ROS1 positive non-small cell lung cancer reach significant benefits from targeted therapy with ALK and ROS1 tyrosinkinase inhibitors. In ALK positive advanced non-small cell lung cancer international guidelines recommend to treat with crizotinib, ceritinib or alectinib, while in cases of failure of this therapy, brigatinib should be the second line biologic treatment. In ROS1 positive advanced NSCLC, crizotinib or ceritinib are recommended accordingly to international guidelines. However, in the Czech Republic, there is no approval of those drugs in first line setting.
ENTIRE ARTICLE
In a review author present the state - of the art of diagnostics and therapy of advanced non-small cell lung cancer with ALK and ROS1 genes rearrangements. Diagnostic processes are realized in specialized pathologic departments with the help of histology, imunohistochemistry and fluorescent in situ hybridization. Patients suffering by either with ALK positive NSCLC, or ROS1 positive non-small cell lung cancer reach significant benefits from targeted therapy with ALK and ROS1 tyrosinkinase inhibitors. In ALK positive advanced non-small cell lung cancer international guidelines recommend to treat with crizotinib, ceritinib or alectinib, while in cases of failure of this therapy, brigatinib should be the second line biologic treatment. In ROS1 positive advanced NSCLC, crizotinib or ceritinib are recommended accordingly to international guidelines. However, in the Czech Republic, there is no approval of those drugs in first line setting.
Erlotinib in the treatment of advanced non‑small cell lung cancer – present experience and results in the Czech Republic
04/2018 MUDr. Helena Čoupková, Mgr. Renata Chloupková, Marek Konečný, Mgr. Magda Bařinová, prof. MUDr. Jana Skřičková, CSc., prof. MUDr. Miloš Pešek, CSc., prof. MUDr. Vítězslav Kolek, DrSc., doc. MUDr. František Salajka, CSc., doc. MUDr. Milada Zemanová, CSc., MUDr. Leona Koubková, MUDr. Libor Havel, MUDr. Kateřina Košatová
Erlotinib is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine-kinase activity, a potent drug in non-small-cell lung cancer (NSCLC) treatment. In this paper, we report a population of patients suffering from advanced NSCLC who are being treated with erlotinib in the Czech Republic under the terms of the TULUNG drug registry (excluding the patients from the University Hospital of Ostrava). By October 2nd 2017, 3763 patients were treated with erlotinib in this cohort. The overall response rate (ORR) in the entire group was 8,7 %, the disease control rate was 58,5 %. Survival data were updated on May 21st 2018. Progression-free survival and overall survival were 3,1 months and 7,7 months, respectively. In our evaluation, we noticed a statistically significant difference both in overall survival (OS) and progression free survival (PFS) in patients grouped according to status of EGFR mutation, performance status, gender and smoking habits. Moreover, there was a statistically significant difference in PFS among patients grouped according to treatment line. Based on our results, skin toxicity appears to be a prognostic factor. The efficacy difference in squamous and non-squamous carcinomas was not statistically significant. From the 3763 patients included in the safety analysis, 1592 (42,3 %) experienced therapy-related adverse events, the most common was rash (35,3 %) and diarrhea (16,3 %). Serious adverse events (G3/4) were reported in 13,6 % patients, the most common was rash (9 %) and diarrhea (3 %). Our results confirm the efficacy and safety of the erlotinib therapy in the first and in the following lines of advanced NSCLC.
ENTIRE ARTICLE
Erlotinib is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine-kinase activity, a potent drug in non-small-cell lung cancer (NSCLC) treatment. In this paper, we report a population of patients suffering from advanced NSCLC who are being treated with erlotinib in the Czech Republic under the terms of the TULUNG drug registry (excluding the patients from the University Hospital of Ostrava). By October 2nd 2017, 3763 patients were treated with erlotinib in this cohort. The overall response rate (ORR) in the entire group was 8,7 %, the disease control rate was 58,5 %. Survival data were updated on May 21st 2018. Progression-free survival and overall survival were 3,1 months and 7,7 months, respectively. In our evaluation, we noticed a statistically significant difference both in overall survival (OS) and progression free survival (PFS) in patients grouped according to status of EGFR mutation, performance status, gender and smoking habits. Moreover, there was a statistically significant difference in PFS among patients grouped according to treatment line. Based on our results, skin toxicity appears to be a prognostic factor. The efficacy difference in squamous and non-squamous carcinomas was not statistically significant. From the 3763 patients included in the safety analysis, 1592 (42,3 %) experienced therapy-related adverse events, the most common was rash (35,3 %) and diarrhea (16,3 %). Serious adverse events (G3/4) were reported in 13,6 % patients, the most common was rash (9 %) and diarrhea (3 %). Our results confirm the efficacy and safety of the erlotinib therapy in the first and in the following lines of advanced NSCLC.
Management of diarrhea as an undesirable effect of treatment with afatinib – case report
06/2017 MUDr. Gabriela Krákorová, Ph.D., MUDr. Hynek Mírka, Ph.D., prof. MUDr. Miloš Pešek, CSc.
Afatinib is an oral preparation, a tyrosine kinase inhibitor of the second-generation EGFR. It is used in the treatment of unresectable locally advanced or metastatic non-small cell lung carcinoma in patients with positive mutations in the gene encoding the epidermal growth factor receptor (EGFR). Afatinib as the first tyrosine kinase inhibitor EGFR demonstrated overall survival compared to chemotherapy in patients with positive EGFR mutation on exon 19 (prolongation of median survival by 12.2 months using afatinib). The most common side effects are rash, diarrhea, stomatitis and paronychia. To cope with side effects, patients need to be cooperative and well informed. At the clinic of pneumology and phthisiology, we have witnessed a brief written lesson that is part of a medical report. In the case of diarrhea, adequate hydration, dietary precautions, and the use of loperamide, which should be provided to patients immediately upon initiation of treatment with afatinib. The case study demonstrates good controlled side effects in collaborating patients with high adherence to treatment. In line with the literature, a good therapeutic effect remains unaffected even when reducing the daily dose of afatinib by half.
ENTIRE ARTICLE
Afatinib is an oral preparation, a tyrosine kinase inhibitor of the second-generation EGFR. It is used in the treatment of unresectable locally advanced or metastatic non-small cell lung carcinoma in patients with positive mutations in the gene encoding the epidermal growth factor receptor (EGFR). Afatinib as the first tyrosine kinase inhibitor EGFR demonstrated overall survival compared to chemotherapy in patients with positive EGFR mutation on exon 19 (prolongation of median survival by 12.2 months using afatinib). The most common side effects are rash, diarrhea, stomatitis and paronychia. To cope with side effects, patients need to be cooperative and well informed. At the clinic of pneumology and phthisiology, we have witnessed a brief written lesson that is part of a medical report. In the case of diarrhea, adequate hydration, dietary precautions, and the use of loperamide, which should be provided to patients immediately upon initiation of treatment with afatinib. The case study demonstrates good controlled side effects in collaborating patients with high adherence to treatment. In line with the literature, a good therapeutic effect remains unaffected even when reducing the daily dose of afatinib by half.
Crizotinib – still „gold standard“ for patients with pulmonary adenocarcinoma with ALK translocation?
06/2017 MUDr. Martin Svatoň, prof. MUDr. Miloš Pešek, CSc.
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 in the first as well as the second line of treatment. Its toxic profile is acceptable and usually well manageable. In the Czech Republic, due to the form of payment, it has been used exclusively in the second line, where we document the experience from our workplace with this drug. Currently, other drugs (ceritinib, alectinib) have proven to be effective in patients with ALK translocations, when it is a question of choosing a treatment plan, which is discussed in more detail in the discussion.
ENTIRE ARTICLE
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 in the first as well as the second line of treatment. Its toxic profile is acceptable and usually well manageable. In the Czech Republic, due to the form of payment, it has been used exclusively in the second line, where we document the experience from our workplace with this drug. Currently, other drugs (ceritinib, alectinib) have proven to be effective in patients with ALK translocations, when it is a question of choosing a treatment plan, which is discussed in more detail in the discussion.