Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play an important role in the pathogenesis of non-small cell lung cancer. Because these alterations are so-called targetable mutations, their identification is important in daily clinical practice. The diagnostic standard of EGFR mutations is currently based on polymerase chain reaction methods, particularly the quantitative real-time polymerase chain reaction. In recent years, new generation sequencing has become increasingly important. In patients with EGFR mutations, a significant improvement in therapeutic outcomes was achieved with the administration of targeted therapy using tyrosine kinase inhibitors. EGFR is composed of four domains: extracellular with a ligand binding site, a transmembrane domain, a cytoplasmic tyrosine kinase catalytic domain, and a C-terminal domain. The key structures of the tyrosine kinase domain responsible for signal activation and transmission are encoded within exons 18-21 on chromosome 7. EGFR mutations are highly heterogeneous. About 90% of EGFR mutations are deletions of exon 19 and point mutation L858R in exon 21. These are referred to as classic mutations. Approximately 10% of the total number of EGFR mutations is attributable to less frequent alterations in the EGFR gene. Due to the low incidence of non-small cell lung cancer with less frequent EGFR mutations, information on their predictive significance is still incomplete. Most of the data for the treatment of cases with uncommon mutations were gathered from retrospective analyses and evaluations of small cohorts. PURPOSE: The aim of this review is to summarise the current options for diagnosing and treating non-small cell lung cancer patients with uncommon EGFR mutations. This work was supported by the MEYS - NPS I - LO1413 and MH CR - DRO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 2. 6. 2019 Accepted: 26. 8. 2019.

Association of the postoperative white blood cells (WBC) count in peripheral blood after radical surgical treatment of left upper lobe non-small cell lung cancer (NSCLC) with overall survival - single center results.

INTRODUCTION: The individual patient prognosis after radical surgery for Non-small cell lung cancer (NSCLC) of left upper lobe remains still unclear. The purpose of this study is to evaluate the predictive value of elevated white blood cell count in peripheral blood as early indicator of postoperative NSCLC prognosis. METHODS: A retrospective statistical analysis was performed studying patients subject to radical treatment of left upper lobe NSCLC in period of five years with subsequent one to three-year monitoring of morbidity and mortality of the patient population. The statistical ROC (Receiver Operating Characteristic) analysis of the WBC count in peripheral blood third day after the operation was used to evaluate the relationship with overall survival, with respect to patients surviving for at least 24 months. RESULTS: Based on the results of the ROC analysis with a total area under the curve (AUC) of 0.67, it is possible to confirm that the WBC count established third day after the operation allows us to classify patients into groups according to the 24-month overall survival. CONCLUSION: Our findings confirm the potential of using WBC count to improve current protocols to establish postoperative prognosis for NSCLC of the upper left lobe (Tab. 2, Fig. 1, Ref. 11).

[Metachronous lung metastases of mammary carcinoma, or dual malignancy? a surgeons and oncologists point of view case report]. / Metachronní plicní metastázy mamárního karcinomu nebo duplexní malignita? Pohled chirurga a onkologa kazuistika.

Synchronous and metachronous metastases significantly diminish the possibility of remission from cancer. Therefore, therapy needs to be highly effective and strictly individualised. The authors present a case report of a female patient after radical mastectomy due to breast cancer with incidental detection of peripheral lung carcinoid. The aim of the case report is to inform about current trends in primary lung carcinoid therapy through a surgeons and oncologists point of view.

[Iris metastasis as the first sign of small-cell lung carcinoma with metastatic involvement of the mediastinum]. / Duhovková metastáza jako iniciální manifestace bronchogenního malobunecného karcinomu diseminovaného do mediastina.

BACKGROUND: We present the case of small-cell lung carcinoma metastatic to the iris, the course of the disease and management options. CASE: A 69-year-old female was diagnosed with a solid, amelanotic iris mass in her left eye. Differential diagnostics and ancillary tests subsequently led to the diagnosis of disseminated small-cell lung carcinoma. Systemic chemotherapy was indicated after fine needle biopsy verification of metastatic lung cancer. Iris metastasis responded well to the chemotherapy, its regression was observed and secondary open-angle glaucoma was controlled as well. Good visual functions were preserved during the treatment. CONCLUSIONS: Metastatic carcinoma of the iris may be the first sign of disseminated malignant disease. Small-cell lung carcinoma iris metastasis can be treated with chemotherapy. This treatment preserved visual functions, which enhanced the patient's quality of life.

High dose rate intraluminal brachytherapy in the treatment of malignant airway obstructions.

Endobronchial brachytherapy has been increasingly used in an effort to improve local control and relieve symptoms of malignant airway obstructions. Results of the high dose rate (HDR) intraluminal brachytherapy in 67 patients with inoperable endobronchial tumor treated by combination of teletherapy and brachytherapy with curative (group A ) or palliative (group B) intent, patients with recurrent tumors after previous radiotherapy treated by endobronchial brachytherapy alone (group C), and patients treated by brachytherapy without teletherapy (group D) are presented. Symptomatic improvement was achieved in 66%, 74%, 64% and bronchoscopic response in 70%, 85%, 78% of patients in groups A, B and C, respectively. Median survival was 365, 242 and 884 days from diagnosis and 245, 151 and 153 days from the first brachytherapy application in groups A, B and C, respectively. In group D complete bronchoscopic response was achieved in 3 of 4 patients with early tumor and partial response in 6 of 7 patients with advanced disease. We observed 4 acute and 9 late complications. Brachytherapy is an effective palliative treatment of malignant airway stenosis, but the effect on survival is not apparent.

Detection of Bronchial Neoplasia in Uranium Miners by Autofluorescence Endoscopy (SAFE-1000).

The increase in the detection rate for premalignant changes of bronchial epithelium was studied in 56 symptom-free volunteers from the risk group of Czech uranium miners (mean age 50.69 years, mean WLM 21.06 (1 Working Level Month is equal to the absorption of latent energy of 2.08 x 10(-5) J/m(3) in one month, i.e. 170 working hours)) by the additional employment of the System of Autofluorescence Endoscopy (SAFE-1000 Pentax) to conventional white-light bronchoscopy, comparing results with those of bronchial biopsy histopathology examination. Histopathology using hematoxylin and eosin staining confirmed intraepithelial neoplasias in 15 areas in 10 persons. White-light bronchoscopy sensitivity was 21.05%, and specificity 93.7% which an autofluorescence bronchoscopy sensitivity was 78.95% and specificity 81.89%.

[Treatment of inoperable non-small cell bronchogenic carcinoma with a combination of cisplatin and vinorelbine--preliminary evaluation]. / Lécba neoperabilního nemalobunecného bronchogenního karcinomu kombinací cisplatiny a vinorelbinu--prubezné hodnocení.

The optimal therapeutic approach to patients with inoperable non-small-cell carcinoma is still a matter of discussion. The reason is that chemotherapy improves the quality of life only in some patients. It prolongs their life only by several weeks. In recent years in this indication a new cytostatic is tested--vinorelbine which when used in monotherapy achieves a therapeutic response in 16--30%. In clinical trials of phase 2 a combination of vinorelbine and cisplatinum was most effective and therefore it was selected for the third phase of clinical trials. In the Czech Republic a clinical investigation was made with the objective to verify published data on the success of treatment, evaluate undesirable effects and consider whether it is suitable for routine use. Cisplatinum (Platidiam Lachema) was administered--80 mg/m2 on the first day, vinorelbine (Navelbine Pierre Fabre)--30 mg/m2 on the first and eighth day. The cycle was repeated on the 22nd day. All patients were treated for 12 weeks. Then followed the first evaluation and treatment was continued only in patients with regression or stabilization of the disease. In the group of 126 patients in 44 (35%) partial and in 3 (2.3%) complete therapeutic responses were obtained. In 35 (27%) the disease was evaluated during treatment as stabilized, in 38 (30%) of the patients the disease progressed despite treatment. The tolerance of treatment was, when effective antiemetic treatment was used (ondansetrone or granisetrone), relatively satisfactory.

Vinorelbine and cisplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter Czech study.

There is continuous discussion about the optimal treatment for patients with inoperable non small cell lung cancer. This is because chemotherapy can only improve the quality of life in a fraction of treated patients while prolonging survival by a couple of weeks at best. The new cytostatic drug "vinorelbine" has been tested in this indication during the last years. The drug has reached the response rate of 16 to 30% when used as monotherapy. The phase II studies proved the combination of vinorelbine with cisplatin to be the most efficient one and this combination was picked up for phase III clinical trials. The clinical trial with the aims to verify published data on treatment efficacy, to assess adverse effects of treatment and to evaluate appropriateness for routine application has been made in the Czech Republic. The treatment schedule was as follows: cisplatin (Platidiam Lachema) in a dose of 80 mg/m2 on day 1, vinorelbine (Navelbine Pierre Fabre) in a dose of 30 mg/m2 on days 1 and 8. The whole cycle was repeated on day 22. The treatment was applied for 12 weeks. After that the efficacy of treatment was evaluated and only the patients with regression or stabilization of the disease continued the treatment. 44 (35%) partial remissions and 3 (2.3%) complete remissions were achieved in a group of 126 evaluable patients. The effect of treatment was evaluated as stable disease in 35 (27%) patients while the progression of disease occurred in 38 (30%) patients. The tolerance of treatment using effective antiemetic support (ondansetron or granisetron) was fairly good.