Serum albumin is a strong predictor of survival in patients with advanced-stage non-small cell lung cancer treated with erlotinib.

Molecular targeted therapy based on tyrosine kinase inhibitors (TKI), directed at epidermal growth factor receptor (EGFR) is one of the novel effective agents in management of advanced-stage of Non Small Cell Lung cancer (NSCLC). However several candidate predictors have been extensively studied, apart from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been validated. The aim of our retrospective study was to evaluate the association of baseline serum albumin with outcomes in a large cohort of patients with advanced-stage NSCLC treated with erlotinib. Clinical data of 457 patients with locally-advanced (III B) or metastatic stage (IV) NSCLC treated with erlotinib were analysed. Serum samples were collected and the measurement was performed one day before the initiation of erlotinib treatment. Before the treatment initiation, low albumin was (<35 g/l) measured in 37 (8.1%) patients and normal albumin (≥ 35 g/l) was measured in 420 (91.9%). The median PFS and OS for patients with low serum albumin was 0.9 and 1.9 months compared to 1.9 and 11.4 months for patients with normal serum albumin (p=0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that EGFR mutation status (HR=2.50; CI: 1.59-3.92; p<0.001) and pretreatment serum albumin (HR=1.73; CI: 1.21-2.47; p=0.003) were significant independent predictive factors for PFS, whereas EGFR mutation status (HR=3.14; CI: 1.70-5.81; p<0.001), stage (HR=1.48; CI: 1.09-2.02; p=0.013), ECOG PS (HR=1.77; CI: 1.37-2.29; p<0.001) and pretreatment serum albumin (HR=4.60; CI: 2.98-7.10; p<0.001) were significant independent predictive factors for OS. In conclusion, the results of present retrospective study indicate that pretreatment hypoalbuminemia is associated with poor outcome of NSCLC patients treated with erlotinib. Based on these results, measuement of serum albumin is an objective laboratory method feasible for estimation of prognosis of patients with advanced-stage NSCLC.

[Campylobacteriosis at the Department of Infectious Diseases of the University Hospital Brno in 2011-2013: a retrospective study]. / Kampylobakteriózy na Klinice infekcních chorob Fakultní nemocnice Brno v letech 2011-2013: retrospektivní studie.

OBJECTIVE: To provide basic clinical, laboratory, and microbiological characteristics of adult patients with campylobacteriosis admitted to the Department of Infectious Diseases University Hospital Brno (UHB), in 2011-2013. MATERIALS AND METHODS: A retrospective analysis of clinical and laboratory parameters of 160 patients hospitalized with campylobacteriosis at the Department of Infectious Diseases, UHB from 1 January 2011 to 31 December 2013. RESULTS: There was no lethality or bacteremia reported in the study group of 160 adult patients (n=160) with campylobacteriosis. A more severe form of the disease with signs of systemic inflammatory response syndrome (SIRS) occurred in 24 patients, i.e. 15% of the study population. Transient mild to moderate leukocytopenia and thrombocytopenia were seen in 16 (10.0%) and 24 patients (15.0%), respectively, and seven patients (4.4%) had bicytopenia. The following factors correlated statistically significantly with the intestinal form of the disease and SIRS: age under 70 years (p=0.037), absence of arterial hypertension (p=0.044), immunosuppressive treatment (p=0.008), leukocyte count in the peripheral blood over 12.0×10(9)/l (p=0.023), and body temperature over 38.0 °C (p<0.001). Antibiotic treatment was used in 96.3% of patients with the intestinal form and in 100.0% of patients with SIRS. The average duration of antibiotic treatment was 8.8 and 9.3 days, respectively. Postantibiotic colitis due to Clostridium difficile occurred in seven patients (4.4%). There were no organ or autoimmune complications observed. CONCLUSIONS: Campylobacteriosis with SIRS occurs preferentially in persons under 70 years of age. Empirical antibiotic treatment is used too frequently without being adequately deescalated.

Long term experience of patients with unresectable or metastatic KIT positive gastrointestinal stromal tumours.

A retrospective analysis of consecutive patients (183 in total, of which 105 were males and 78 females) with gastrointestinal stromal tumour (GIST) was performed. The mean age was 61 years, median age 64 years. The most frequent localization of the tumour was stomach in 74 patients (40.4 %) and the small intestine in 46 patients (25.1 %). Two or more different synchronous or metachronous cancers occurred in 34 (18.6 %) patients with histologically confirmed GIST. Ninety-six patients were treated with imatinib mesylate in palliative setting during the course of their disease. The therapy was finished in 60 patients and 36 patients have been treated so far. The median progression-free survival reached 32.9 months in the group of 96 patients treated with imatinib. The median overall survival in the group of 96 patients treated for metastatic disease reached 77 months. Two-year and 5-year survival was 85.2 % and 63.1 %, respectively. The second-line therapy with sunitinib malate was administered in 37 patients, of which 31 finished and 6 continued in the therapy. The median progression free survival and median survival since the sunitinib therapy initiation reached 8.4 and 22.1 months, respectively (Tab. 2, Fig. 2, Ref. 16).

Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 -  analysis of the Czech National Cancer Registry.

BACKGROUND: Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. PATIENTS AND METHODS: Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. RESULTS: Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively. CONCLUSIONS: The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.

Prognostic factors in renal cell carcinoma patients treated with sorafenib: results from the Czech registry.

The aim of this study was to describe the characteristics and outcomes of a large cohort of patients treated with sorafenib in clinical practice and to identify predictive factors associated with prognosis. Patient data were obtained from the national Czech registry (RenIS). Data of virtually all Czech patients receiving targeted therapies are entered into this non-interventional post-registration database. Demographics and clinical data, as well as all treatment sequences and clinical outcomes, are reported in this registry. A total of 836 patients treated with sorafenib before March 2013 were included in the analysis. Median age was 63 years and 70% were men. Most patients had received prior treatment with cytokines, sunitinib or both. Sorafenib was the first-line treatment in 15% of patients. Median overall survival and progression-free survival were 21.7 months and 7.5 months, respectively. Median overall survival and progression-free survival was 26.3 and 8.3 months, respectively, in patients receiving sorafenib as first-line therapy. Cox proportional models identified several parameters associated with poor outcome including time ≤1 year from diagnosis to first-line systemic treatment, performance status ≥2, low hemoglobin, and LDH >1.5 times the upper limit of normal. Our data demonstrate that the outcomes of real-life patients are comparable to those enrolled in clinical trials. Prognostic factors identified in the present study were consistent with previously reported models.

[Infections caused by non-typhi serovars of Salmonella at the Infectious Diseases Clinic of the University Hospital Brno in 2011-2013]. / Infekce zpusobené netyfovými sérovary salmonel na Klinice infekcních chorob Fakultní nemocnice Brno v letech 2011-2013--retrospektivní studie.

INTRODUCTION: The aim of the study is to describe the basic clinical, laboratory, and microbiological characteristics in adult patients with salmonellosis hospitalized at the Infectious Diseases Clinic of the University Hospital Brno in 2011-2013. MATERIALS AND METHODS: A retrospective analysis of clinical and laboratory parameters of 161 patients hospitalized at the Infectious Diseases Clinic of the University Hospital Brno from 1 January 2011 to 31 December 2013. RESULTS: Invasive salmonellosis was seen in 22.4% of the study group. The overall lethality rate reached 3.1%. Treatment with antibiotics was used in 93.8% of patients. Transient mild to moderate leukocytopenia was reported in 4.3% of patients and thrombocytopenia in 9.3% of patients. Transient changes in white blood cells as well as in the thrombocyte count were not clinically important. Long-term treatment with proton pump inhibitors is a risk factor for salmonellosis (p=0.128), but not for invasive salmonellosis. Long-term use of opioids (p=0.003) and/or acetylsalicylic acid (p=0.015) is a risk factor for invasive salmonellosis. Other risk factors for invasive disease are: age over 70 years (p=0.011), arterial hypertension (p=0.004), disease duration of less than three days (p=0.006), serum creatinine level above 250 µmol/l (p=0.01), peripheral leucocyte count above 12x10(9)/l (p=0.001), and body temperature above 38 °C (p=0.001). Hypokalemia does not represent a risk factor for invasive salmonellosis. CONCLUSIONS: Aged patients on long-term opioids or acetylsalicylic acid, with disease duration of less than three days, and meeting the criteria for systemic inflammatory response syndrome are at the highest risk for invasive salmonellosis. Empirical antibiotics are prescribed too often and the treatment is not properly de-escalated.

Tobacco dependence, the most important cardiovascular risk factor: treatment in the Czech Republic.

Smoking is the most important cardiovascular (CV) risk factor. Stopping smoking halves the CV risk. Every clinician should provide a brief intervention with smokers. Intensive treatment should be available to those who need it. There are 37 Centers for Tobacco Dependence in the Czech Republic, which offer treatment including a psychobehavioral intervention and pharmacotherapy (varenicline, nicotine, bupropion). Czech physicians, pharmacists and nurses are regularly educated about smoking cessation. We describe the results of intensive treatment offered by our centers. Treatment includes screening (1 h), an intervention (2 h), and follow-up visits during the next 12 months. Among 3532 patients, 34.3 % had CO-validated abstinence at 12-months (including 489 patients who attended the screening visit + only the 12-month follow up visit). Among patients who underwent the intervention, the abstinence rate was 38.2 %. The majority of patients who underwent the intervention (N=2470) used some form of pharmacotherapy. After one year, the abstinence rate was 43.4 %, compared to 15.9 % (N=573) without pharmacotherapy. Only 28 % of patients came on the recommendation of a physician. Despite the decrease in CV risk following smoking cessation and the effectiveness of treatment, centers are underutilized.

Epidemiological factors influencing the development of relapsing and severe Clostridium difficile infection.

INTRODUCTION: Clostridium difficile infection (CDI) is currently the most frequent cause of nosocomial infectious diarrhea in adults in the developed countries. The goal of the study was to evaluate risk factors for relapsing and severe CDI in a set of patients hospitalized at the Clinic of Infectious Diseases at the University Hospital Brno. MATERIALS AND METHODS: A retrospective analysis of epidemiological, clinical and laboratory data of 281 patients with proved CDI diagnosis hospitalized in the period from 1. 1. 2007 to 31. 12. 2010. RESULTS: Patient age over 65 is a risk for severe CDI (OR 2.95, p < 0.001) and extends hospitalization at the first episode of CDI by about 3.2 days on average. Patients with 2 or more comorbidities (p < 0.05) or with a history of recent hospitalization (p 0.001) are at risk for both relapsing CDI and severe CDI. The use of proton pump inhibitors may increase the number of relapses (OR 1.94, p < 0.05). If the CDI symptoms appear within 7 days of taking antibiotics, there is a greater risk of relapse (OR 2.32, p < 0.05). If the symptoms occur after a longer period, a mild or moderate course of the disease can be expected (OR 0.31, p < 0.05). CONCLUSIONS: To determine the risk level for development of relapsing or severe CDI, focus on risk factors from the patients medical history and their clinical and laboratory status is appropriate at the outset of CDI patients treatment. An early intensive monitoring of vital functions and administration of aggressive treatment can reduce complications, mortality and relapses of CDI.

[Smoking and postoperative complications]. / Kourení a pooperacní komplikace.

INTRODUCTION: Smoking has a negative impact on the outcome of surgical procedures. Smoking leads to higher risk of postoperative complications and it delays wound healing. MATERIALS AND METHODS: We observed pulmonary complications, wound healing complications, and the length of the postoperative hospitalization period of 877 patients admitted for elective surgery.. Patients were divided according to their smoking status in to 3 groups: the current smokers were 32% (279/877), the former smokers 31% (274/877) and the non-smokers 37% (324/877). RESULTS: Pulmonary complications occurred more frequently in the smoking group (3.9%) compared to the non-smoking group (0.9%), p<0,001. The incidence of wound infections was 7.5% in the smoking group compared to 4.6% in the non-smoking group. Wound dehiscence occurred in 3.6% patients in the smoking group, respectively 2.8% in the non-smoking group, without statistical significance. The number of postoperative hospitalisation days was 3 days for both smokers and non-smokers, but it decreased inversely to number of smoke-free days before the surgery for those who stopped smoking: those abstinent for 31-90 days were hospitalized for 7.0 days, those abstinent for 91-183 were hospitalized for 5.5 days, and for those abstinent over 184 days the postoperative hospitalization was, again, 3 days. Among the current smokers, 93% preferred to stay smoke-free after the surgery. CONCLUSIONS: Our results support better surgery outcomes for non-smokers. However, our sample was not large enough to assess the impact of the number of preoperative smoke-free days. An elective surgery seems to be an unused occasion to motivate smokers to stop smoking, preferably, as soon as possible before the surgery date.

Erlotinib in the treatment of advanced squamous cell NSCLC.

Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC). We conducted a large retrospective study based on clinical experience aiming to prove erlotinib's efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity. 1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P<0.001). OS of patients with CR/PR, SD and PD were 13.3, 10.9 and 3.8 months, respectively (P<0.001).The most common adverse effects were rash and diarrhoea. In conclusion ertlotinib is effective and well-tolerated in patients with advanced-stage squamous cell NSCLC.

Czech adolescent smokers: unhappy to smoke but unable to quit.

OBJECTIVE: To assess the prevalence of tobacco dependence among adolescents in the Czech Republic in 2010, their willingness to quit and knowledge about quitting options. METHODS: Primary, intermediate and secondary school students completed an anonymous questionnaire on tobacco use during a smoking prevention class, with a response rate of 100%. RESULTS: Of 1420 anonymous questionnaires analysed, 66.8% (n = 949) of respondents had ever tried smoking. More were from smoking (50.4%) than non-smoking (49.6%) families; there were no differences in sex. Most student smokers had experimented with cigarettes (94.6%), cigars (8%), marihuana cigarettes (4.6%) and water pipes (1.9%). At the time of the survey, 52.9% (520/949) of those who had ever tried smoking were current smokers, 30.3% smoked daily, 18.3% weekly and 4.2% less frequently. Only 20.5% of smokers had not considered quitting, and 66.9% had tried unsuccessfully to quit. Withdrawal symptoms were experienced by 24.5% (123/502) of the current smokers, indicating a high level of nicotine dependence in this age group. The majority (346/467, 74.1%) of the current smokers said they would stop smoking immediately on their own. Only a few would seek help at a pharmacy (4.9%), 3.4% would ask their doctor and 1.7% their parents. CONCLUSIONS: Tobacco dependence is prevalent among Czech adolescents. The majority of smokers wanted to stop, but knowledge about smoking cessation and quitting assistance offered to smokers was low.

[Epidemiological and clinico-pathological characteristics of patients with renal carcinoma: a single institution analysis of 544 cases]. / Epidemiologická a klinicko-patologická charakteristika pacientu s renálním karcinomem: analýza 544 prípadu z jednoho centra.

BACKGROUND: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. PATIENTS AND METHODS: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. RESULTS: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. CONCLUSION: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.

Comparison of EGFR-TKI and chemotherapy in the first-line treatment of advanced EGFR mutation-positive NSCLC.

Molecular targeted therapy based on EGFR tyrosine kinase inhibitors (EGFR-TKI) is currently astate of the art option for management of advanced stage NSCLC. Activating EGFR mutations are preferable for a good treatment response to EGFR-TKI. The presented retrospective study evaluated a clinical observation of EGFR-TKI aiming at its efficacy and safety in comparison to a standard chemotherapy in the first-line treatment of advanced stage NSCLC. Total number of patients with advanced stage (IIIB, IV) EGFR mutation-positive NSCLC was 54 of which 23 were treated with EGFR-TKI and 31 patients with various chemotherapy regimens in the first line. The treatment efficacy was characterized in terms of disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). The comparison of DCR was performed using Fisher's exact test and the differences in survival were tested using log-rank test. DCR for EGFR-TKI treatment was 95.6% vs. 70.9% for chemotherapy (p=0.032). Median of PFS in patients treated with EGFR-TKI was 7.2 months vs. 2.5 months in patients treated with chemotherapy (p<0.001). Median of OS was 14.5 months vs. 21.4 months (p=0.729). EGFR-TKI was associated with higher incidence of skin rash and diarrhoea; chemotherapy was associated with higher incidence of haematologic adverse events and nausea or vomiting. The analysis results showed a favourable DCR and PFS in patients treated with EGFR-TKI in the first line. The non-significant difference in OS could be attributed to a cross-over during the patient follow-up as well as the differences in performance status and age between both groups. EGFR-TKI is the optimal choice for the first-line treatment of EGFR mutation-positive NSCLC.

[Risk factors for relapsing and severe colitis caused by Clostridium difficile infection]. / Rizikové faktory rekurentního a tezkého prubehu kolitidy vyvolané infekcí Clostridium difficile.

BACKGROUND: Describe risk factors for relapsing and severe Clostridium difficile infection (CDI) in a set of patients hospitalized at the Clinic of infectious diseases the University Hospital Brno. MATERIAL AND METHODS: A retrospective study observing epidemiological, clinical and laboratory data of 281 patients with proven diagnosis of Clostridium difficile infection hospitalized in the period from 1. 1. 2007 to 31. 12. 2010. RESULTS: In the first part of the evaluation were enrolled 233 patients, 87 (37.3 %) patients had a record of relapsing CDI and 146 (62.7 %) patients had nonrelapsing CDI. Factors associated with relaps included 2 or more comorbidities, previous hospitalization during the 4 weeks before CDI, the use of proton pump inhibitors. In the second part of the evaluation were enrolled all 281 patients, severe CDI during any episode of the disease was observed in 181 (64.4 %) patients, while the remaining 100 (35.6 %) patients had mild or moderate CDI. The risk factors associated with severe CDI were age older than 65 years, history of coronary heart disease, chronic renal insufficiency, a combination of 2 or more comorbidities, previous hospitalization in a period of 4 weeks. CONCLUSIONS: Age older than 65 years is the risk for severe CDI. Patients with 2 or more comorbidities or with history of previous hospitalization are in a risk for both, relapsing and severe CDI. Use of proton pump inhibitors may lead to recurrence, probably on the basis of re-infection Clostridium difficile spores.

Second line treatment in advanced non-small cell lung cancer (NSCLC): comparison of efficacy of erlotinib and chemotherapy.

Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of novel options for management of NSCLC. Erlotinib is EGFR tyrosine kinase inhibitor used for treatment of the advanced NSCLC. This presented study is focused on comparison of erlotinib and chemotherapy efficacy in the second line treatment of the advanced NSCLC. DCR and PFS became the primary endpoints.Total number of patients was 290. A group treated with chemotherapy in the second line consisted of 150 patients and a group treated with erlotinib in the second line consisted of 140 patients. Comparison of DCR was performed using Fisher's exact test, visualization of PFS was performed using Kaplan-Meier survival curves and differences were tested using the log-rank test. Genetic testing was performed using PCR direct sequencing. In the group treated with chemotherapy 2 CR, 23 PR and 51 SD were achieved vs. 5 CR, 10 PR and 55 SD in the group treated with erlotinib in the second line. DCR in patients treated with chemotherapy was 54.0% vs. 51.3% in patients without EGFR mutation treated with erlotinib (p=0.707); in patients harboring EGFR mutation, treated with erlotinib (n=9) outstanding results were achieved: 4 CR, 2 PR and 3 SD (not tested). Median of PFS in patients treated with chemotherapy was 2.1 months vs. 1.9 months in patients without EGFR mutation (p=0.879) vs. 8.4 months in patients harboring EGFR mutation treated with erlotinib (p=0.017). Results of analysis show that even patients without EGFR mutation are able to benefit from erlotinib treatment in the second line. The efficacy (DCR, PFS) of erlotinib in patients without EGFR mutation was comparable with chemotherapy. The treatment efficacy in a subgroup of patients harbouring EGFR mutation treated with erlotinib was significantly better than in patients without EGFR mutation.

Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice.

Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor used in treatment of advanced NSCLC. Patients harboring EGFR or KRAS mutations represent minority of all patients in caucasian population and there is no available predictor for a predominant group of patients harboring the wild-type EGFR and wild-type KRAS genes. Skin rash is the most frequent manifestation of cutaneous toxicity of erlotinib. Rash is associated with a good therapeutic response. We aimed at the evaluation of rash as a predictor of therapeutic effect of erlotinib in patients harboring the wild-type EGFR and KRAS wild-type genes and to assess its possible usage in a clinical practice.Totally 184 patients with advanced stage NSCLC (IIIB, IV) harboring the wild-type EGFR and wild-type KRAS genes were analysed. Comparison of ORR, PFS and OS according to the occurrence of rash was performed. In order to assess the impact of rash in clinical practice it was conducted landmark analysis of the group of patients whose rash was observed during first month of treatment (n=124). Patients in whom progression was observed during the first month of treatment were excluded from the landmark analysis. The comparison of ORR was performed using Fisher's exact test, visualization of survival was performed using Kaplan-Meier survival curves and the differences in survival were tested using the log-rank test. Median PFS in patients who were observed with rash during the treatment was 3.0 vs. 1.2 months in patients with no rash (p<0.001), median of OS in patients who were observed with rash during the treatment was 13.9 vs. 5.8 months in patients with no rash (p<0.001). ORR in patients who were observed with rash during the treatment was 17.4% vs. 3.3% in patients with no rash (p=0.001). Median of PFS after 1 month of treatment in patients who were observed with rash during the first month was 2.9 vs. 1.1 months in patients with no rash (p=0.027). Median of OS after 1 month of treatment in patients who were observed with rash during the first month was 13.8 vs. 9.9 months in patients with no rash (p=0.082). Rash is strongly associated with better survival and ORR in patients harboring wild-type EGFR and wild-type KRAS genes. Occurrence of rash during the first month of treatment is a useful predictor of better effect of erlotinib after one month of treatment. Patients who were not observed with rash during the first month of treatment are in high risk of progression. Optimization of the treatment of these patients can contribute restaging after two months of treatment, assessment of plasma levels of erlotinib and eventually attempt to dose escalation.

[EGFR mutations in patients with advanced NSCLC]. / Mutace genu EGFR u pacientu s pokrocilým NSCLC.

BACKGROUND: Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of novel options for management of NSCLC. EGFR gene mutations, exon 19 deletions and exon 21 point mutations (L858R) are good predictors of response to EGFR-TKI treatment. The aim of this study was to assess the incidence of EGFR mutations in a large cohort of Europeans with advanced NSCLC and subsequently to evaluate their impact on the effect of EGFR-TKI treatment. PATIENTS AND METHODS: In total, 613 patients with advanced stage NSCLC (IIIB, IV) were genetically tested. The effect of treatment was evaluated in 410 patients treated with EGFR-TKI. Survival was evaluated using Kaplan-Meier method, and statistical comparison was performed using log-rank test. RESULTS: EGFR mutations were detected in 73 (11.9%) patients. Exon 19 deletions were detected in 49 patients, exon 21 point mutations (L858R) were detected in 22 patients, and both mutation types were detected in 2 patients. An increased incidence of EGFR mutations among patients with adenocarcinoma (14.9% vs 7.8%, p = 0.008), women (20.2% vs 7.1%, p < 0.001) and nonsmokers (29.9% vs 7.0%, p < 0.001) was demonstrated. Sixty patients with EGFR mutation and 350 patients with wild-type EGFR were treated with EGFR-TKI. Median PFS in patients harboring EGFR mutation was 7.2 vs 2.0 months in patients harboring wild-type EGFR (p < 0.001), median OS in patients harboring EGFR mutation was 14.5 vs 7.5 months in patients harboring wild-type EGFR (p = 0.019). CONCLUSION: The incidence of EGFR mutations in the studied population, their increased incidence among patients with adenocarcinoma, women and non-smokers correlated with data previously published. Results of survival analysis in patients treated with EGFR-TKI confirmed high potential of EGFR mutations to predict good effect of the EGFR-TKI treatment. Genetic testing in patients with NSCLC should be a standard part of diagnostic procedures

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study.

BACKGROUND: A retrospective, registry-based analysis to assess the outcomes of metastatic renal cell cancer (mRCC) patients treated with sunitinib and sorafenib who developed dermatologic adverse events was performed. PATIENTS AND METHODS: Data on mRCC patients treated with sunitinib or sorafenib were obtained from the Czech Clinical Registry of Renal Cell Cancer Patients. Outcomes of patients who developed hand-foot syndrome (HFS) of any grade and/or grade 3/4 rash during the treatment were compared with patients without HFS and no, mild, or moderate rash. RESULTS: The cohort included 705 patients treated with sunitinib and 365 patients treated with sorafenib. For sunitinib, the median overall survival (OS) was 43.0 months versus 31.0 months (P = 0.027) and median progression-free survival (PFS) 20.8 months versus 11.1 months (P = 0.007) for patients with versus without dermatologic toxicity, respectively. For sorafenib, the median OS and PFS were 27.9 and 24.6 months (P = 0.244), and 12.2 and 8.8 months (P = 0.050), respectively. In multivariable Cox regression, the skin toxicity was significantly associated with longer OS in the sunitinib cohort. CONCLUSION: The presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib.