Jana Skrickova

The incidence and predictors of thromboembolic events in patients with lung cancer.

Patients with lung cancer experience elevated risk of venous thromboembolism. Cancer patients with thrombosis have a shorter life expectancy and the occurrence of VTE worsens the quality of life and may delay, interrupt, or completely halt the cancer therapy. In a large cohort of lung cancer patients we monitored the incidence of venous thromboembolism and we identified groups of patients with the highest risk of venous thromboembolism suitable for antithrombotic prophylaxis, which could favourably affect their morbidity and mortality.

TaqMan based real time PCR assay targeting EML4-ALK fusion transcripts in NSCLC.

OBJECTIVES Lung cancer with the ALK rearrangement constitutes only a small fraction of patients with non-small cell lung cancer (NSCLC). However, in the era of molecular-targeted therapy, efficient patient selection is crucial for successful treatment. In this context, an effective method for EML4-ALK detection is necessary. We developed a new highly sensitive variant specific TaqMan based real time PCR assay applicable to RNA from formalin-fixed paraffin-embedded tissue (FFPE). MATERIALS AND METHODS This assay was used to analyze the EML4-ALK gene in 96 non-selected NSCLC specimens and compared with two other methods (end-point PCR and break-apart FISH). RESULTS EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR. All real time PCR positive samples were confirmed with direct sequencing. A total of 46 specimens were subsequently analyzed by all three detection methods. Using variant specific real time PCR we identified EML4-ALK transcript in 17/46 (37%) specimens, using end-point PCR in 13/46 (28%) specimens and positive ALK rearrangement by FISH was detected in 8/46 (17.4%) specimens. Moreover, using variant specific real time PCR, 5 specimens showed more than one EML4-ALK variant simultaneously (in 2 cases the variants 1+3a+3b, in 2 specimens the variants 1+3a and in 1 specimen the variant 1+3b). In one case of 96 EML4-ALK fusion gene and EGFR mutation were detected. All simultaneous genetic variants were confirmed using end-point PCR and direct sequencing. CONCLUSION Our variant specific real time PCR assay is highly sensitive, fast, financially acceptable, applicable to FFPE and seems to be a valuable tool for the rapid prescreening of NSCLC patients in clinical practice, so, that most patients able to benefit from targeted therapy could be identified.

The prevalence of obstructive sleep apnea in patients hospitalized for COPD exacerbation

BACKGROUND The concurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is generally identified as an overlap syndrome. Only limited evidence is available on the prevalence of OSA in patients with stable COPD, and essentially no data on the prevalence of OSA in patients hospitalized for COPD exacerbation. The aims of the study were to determine the ratio of concurrence of OSA in patients hospitalized for COPD exacerbation and to identify the confounders of OSA detected in COPD subjects. METHODS 101 patients were hospitalized for COPD exacerbation at the Department of Respiratory Diseases in the course of four months. Seventy-nine consecutive patients were enrolled in the study and in 35 of these subjects polygraphy was performed. Descriptive statistics, Mann-Whitney test, Kruskal-Wallis test, Spearman correlation and Fishers test were used to summarize and evaluate results. RESULTS In 18 (51.4%) subjects with polygraphy examination, the apnea-hypopnea index (AHI) ≥ 5 indicated the presence of OSA. The AHI value, and thus the severity of the sleep disorder, correlated with the class of the Mallampati score, presence of snoring, apnea, coronary heart disease, diabetes mellitus in patients history, height, body mass index, neck, waist and hip circumferences, and the value of the Epworth sleepiness scale. CONCLUSION Polygraphy performed in patients hospitalized for exacerbation of COPD indicated an increased prevalence of OSA compared to the general population and stable COPD patients.

Nutritional Risk Screening Predicts Tumor Response in Lung Cancer Patients

Background: Malnutrition in cancer patients may be associated with poor tolerance of chemotherapy and lower response rate after oncological treatment. Methods: Nutritional Risk Screening 2002 (NRS) adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 patients with lung cancer. The risk was evaluated on a 6-point scale according to common signs of nutritional status (weight loss, body mass index, and dietary intake), tumor, and its treatment risk factors. A score of 3 or more (called “nutritional risk”) means significant risk of malnutrition and poor outcome. Results: Acceptable NRS score was found in 50.6%, and in 45.3% a score of 3–5 suggested the risk of malnutrition (nutritional risk). Unexpectedly, the toxicity of anticancer treatment was not significantly different between the subgroups (acceptable score vs nutritional risk). The rate of treatment response evaluated by imaging techniques was significantly higher in patients with an acceptable score compared to nutritional risk. Overall survival rate was significantly higher in cytostatically treated patients with lung cancer with an acceptable score. Conclusion: Nutritional risk screening is a significant predictor of tumor response in patients with lung cancer. Early detection of malnutrition is important to determine the prognosis of cancer patients as well as to plan effective supportive care.

Identification of atypical ATRNL1 insertion to EML4-ALK fusion gene in NSCLC

We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALKs sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.

Ice Hockey Lung – A Case of Mass Nitrogen Dioxide Poisoning in The Czech Republic

Nitrogen dioxide (NO₂) is a toxic gas, a product of combustion in malfunctioning ice-resurfacing machines. NO₂ poisoning is rare but potentially lethal. The authors report a case of mass NO₂ poisoning involving 15 amateur ice hockey players in the Czech Republic. All players were treated in the Department of Respiratory Diseases at Brno University Hospital in November 2010 - three as inpatients because they developed pneumonitis. All patients were followed-up until November 2011. Complete recovery in all but one patient was achieved by December 2010. None of the 15 patients developed asthma-like disease or chronic cough. Corticosteroids appeared to be useful in treatment. Electric-powered ice-resurfacing machines are preferable in indoor ice skating arenas.

P39. Management of respiratory symptoms in patients with advanced lung cancer

Lung cancer is the most common cancer worldwide in terms of both incidence and mortality. Prognosis is generally poor. Of all patients with lung cancer, approximately 15% survive for 5 years after diagnosis while 80% die within 1 year. Respiratory symptoms observed in patients with lung cancer (dyspnea, cough, haemoptysis) are determined by cancer’s histologic type, biological properties, and anatomic location. They may be caused either by the primary tumour itself or by locoregional metastases within the thorax. Respiratory symptoms can result from immediate mechanical effects of cancer spread, such as localized obstruction of large airways, postobstructive pneumonia, formation of fistulae between airways and other intrathoracic structures, pleural effusion, and paresis of diaphragm or vocal cords due to encroachment upon respective nerves. In such patients, noninvasive therapies may be insufficient to palliate respiratory symptoms. Invasive techniques are available to benefit this group of patients. Respiratory symptoms can be caused by chemotherapy, or complications of radiotherapy (airway stenosis and necrosis, fistula formation, haemoptysis). Moreover, comorbid conditions such as chronic obstructive lung disease (COPD), heart failure, pulmonary embolism, previous lung resection or malnutrition likewise contribute to respiratory symptoms. Dyspnea is the most frequently reported symptom in lung cancer patients: over of 65% patients have this symptom at some time during the course of their illness. In management of cancer-related dyspnea, opioids will remain the mainstay of therapy for the foreseeable future. Further studies will also be needed to identify the target populations who would benefit from oxygen, benzodiazepines, and the wide spectrum nonpharmacological interventions to relieve dyspnea. The design of these studies should respect the difference between cancer-related dyspnea and dyspnea from other causes. Suppression of cancer-related cough should also be addressed in future randomized studies. Current recommendations for palliative care in patients with advanced lung cancer, organized according to salient respiratory symptoms: Dyspnea: opioids; supplemental oxygen; other pharmacological interverventions; nonpharmacological interventions; dyspnea due to comorbidities and its treatment. Cough: opioids, non-opioid cough supressants, chemotherapy. Haemoptysis: pharmacologic treatment, bronchoscopic management, palliative thoracic radiotherapy. Malignant pleural effusion: thoracocentesis, chest tube dranaige, pleurodesis, and pleuroperitoneal shunting.

Full Oral Vinorelbine (NVBO) on D1 and D8 With Carboplatin (CBDCA) as First Line Treatment in Advanced Non-small Cell Lung Cancer (NSCLC) Patients: Preliminary Results of a Prospective Sudy in Nonrandomized Population

The purpose of this trial was to evaluate the activity and feasibility of CBDCA together with NVBO as first line treatment in patients with advanced NSCLC. METHODS: Patients with advanced NSCLC received NVBO 80 mg/m2 on D1 and D8 with CBDCA AUC5 on D1 every three weeks. In stage III, chemotherapy was followed by external radiotherapy. The outcomes include following: response, median overall survival (mOS) and median progression free survival (mPFS). The difference in response relative to baseline characteristics was determined using Pearson Chi-square test. Differences in OS and PFS relative to baseline characteristics were evaluated for significance using Log-rank test. RESULTS: 259 patients were treated: 209 men (80,7%) and 50 women (19,3%), median age 65 years. ECOG performance status at inclusion was PS 0 in 47 (18,2% patients, PS 1 in 185 (71,7%) and PS 2 in 26 (10,1%) patients. Most patients had stage IIIB 97 (37,5%) and stage IV NSCLC 130 (50,2%), only 32 (12,4%) were stage IIIA . Adenocarcinoma was confirmed in 52 patients (20,1%), squamous-cell carcinoma in 152 (58,7%), large-cell carcinoma in 8 (3,1%) and other in 47 (18,4%). Complete response was confirmed in 1 (0,4%) patient, partial response in 121 (46,7%), stable disease in 58 (22,4%), 79 (30,5%) patients progressed. The regimen was well tolerated. Median cycles was 4, the dosage of NVBO was without changes in 159 (61%) patients, the dosage of NVBO was reduced in 12 (4,7%) and escalated in 64 (24,8%). In 23 (8,9%) of patients was the dosage of NVBO reduced after escalation. Major toxicities (Grade 3-4) were neutropenia in 69 (26,9%), leucopenia in 51 (19,8%), anemia in 7 (2,7%), and thrombocytopenia in 6 (2,3%) patients. Febrile neutropenia was observed in 17 (6,6%) patients. Gastrointestinal toxicity grade 3-4 was observed in 47 (18,4%) patients. The estimated mOS was 13,8 moths. and the estimated mPFS was 9,4 months by median follow-up 8,5 months. The differences between groups of pts according to PS (0+1 vs. 2) were statistically significant (p < 0,001) better for patiens with PS 0+1. CONCLUSIONS: In this group of 259 non-selected patients with advanced NSCLC was the treatment with full NVBO and CBDCA in first line more convenient and well tolerated with evidence of high antitumour activity. This combination was active in all groups patients according histology.

Pemetrexed in the Second Line Chemotherapy of Non-small Cell Lung Cancer. A Multicentre Prospective Analysis of Data From Clinical Practice

Non small cell lung cancer (NSCLC) is one of the most aggressive tumours with unsatisfactory prognosis and extremely high mortality. Pemetrexed became one of the standard chemotherapeutic options in advanced NSCLC. It is recommended both in the 1st line and in the 2nd line.

Intravenous vinorelbine (NVBiv) on D1 and oral vinorelbine (NVBo) on D8 in combination with carboplatin (CBDCA) as first-line treatment in advanced non-small lung cancer (NSCLC) patients: Results of a prospective study in nonselected population.

The use of intravenous vinorelbine (NVBiv) on D1 and oral vinorelbine (NVBo) on D8 in combination with carboplatin (CBDCA) as first-line treatment in advanced non-small lung cancer (NSCLC) patients: results of a prospective study in nonselected population are reported.