Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC.

Introduction: We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC. Methods: Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m2 (d 1) and 500 mg/m2 (d 8), cisplatin 75 mg/m2 (d 1), and gemcitabine 1250 mg/m2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff. Results: A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%-50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event. Conclusions: The combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155).

SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets.

Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.

Relationship between incidence of chronic obstructive pulmonary disease and lung cancer as comorbidity in primary health care in two Belgrade communities.

PURPOSE: To investigate the recent trends in the incidence of chronic obstructive pulmonary disease (COPD) and lung cancer as comorbidity in primary health care (Community Health Center, Zemun, Belgrade, which covers two municipalities - Surchin and Zemun), during the period 2014-2017. METHODS: This retrospective study analyzed the incidence of COPD and lung cancer as comorbidity in a 4-year period. Data were derived from the Heliant information system. Descriptive statistics -frequencies and percentages - were used, and differences between groups were tested by x2 test. RESULTS: The number of patients with COPD was slightly, but insignificantly, higher each consecutive year. Lung cancer as comorbidity appeared in about 11% of these patients. As for gender, male and female patients contributed equally to the number of patients with CORD. CONCLUSION: The number of patients with COPD registered in primary health care was similar in all investigated years. Lung cancer as comorbidity was found in a significantly smaller number of these patients.

Appearance of ductal breast and colon carcinoma with gastrointestinal stromal tumor (GIST) in a female patient: an extremely rare case.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Very few cases of coexistence of GIST and adenocarcinoma in other organs have been described. CASE PRESENTATION: We present the case of a 63-year-old female patient diagnosed with breast cancer. After five years of the diagnosis, the findings of colon adenocarcinoma and GIST in stage IA were discovered incidentally during surgical treatment of the colon carcinoma. This tumor display: mixed spindle-epithelioid cell cytological type, of moderate cellularity, mitotic index (1∕10) with low anaplasia, low proliferative status (Ki-67 index 12%), without necrosis and immunophenotype profile: antiendomysial antibody (EMA)-, vimentin+++, CD117++, CD34+++, alpha-smooth muscle actin (α-SMA)+, desmin+∕-, S-100-, CD68-. CONCLUSIONS: The present case is extremely rare since the patient has adenocarcinoma with GIST in a previously diagnosed breast carcinoma. Based on this, in clinical practice should always think about possibility occurrence of synchronous and metachronous tumors.

Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity, / Pneumonia adquirida na comunidade: economia de cuidados médicos, em relação à gravidade clínica

Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe. .

Objetivo: Avaliar os custos médicos diretos e indiretos de diagnóstico e tratamento para pacientes com pneumonia adquirida na comunidade (PAC), correlacionando-os com a gravidade da PAC ao diagnóstico e identificando os principais fatores de custo. Métodos: Análise de custos prospectiva utilizando custo bottom-up. A gravidade clínica e o risco de mortalidade foram determinados através de pneumonia severity index (PSI) e a escala mental C onfusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65), respectivamente. A amostra foi composta por 95 pacientes hospitalizados devido a PAC recém-diagnosticada. A análise foi realizada em uma perspectiva social com um horizonte de tempo de um ano. Resultados: Expressos em média ± desvio-padrão em euros, os custos médicos diretos e indiretos por paciente com PAC foram de 696 ± 531 e 410 ± 283, respectivamente, sendo, portanto, o custo total por paciente de 1.106 ± 657. O impacto orçamentário combinado deste grupo de pacientes em euros foi de 105.087 (66.109 e 38.979 nos custos diretos e indiretos, respectivamente). Os principais fatores de custo, em ordem descendente, foram custo de oportunidade (perda de produtividade); diagnóstico e tratamento de comorbidades; e administração de medicamentos, oxigênio e derivados do sangue. Os escores CURB-65 e PSI correlacionaram-se com os custos indiretos do tratamento da PAC. O escore PSI correlacionou-se positivamente com a frequência global no uso de serviços médicos. Nenhum dos escores mostrou uma relação clara com os custos diretos do tratamento da PAC. Conclusões: A gravidade clínica na admissão parece não se correlacionar com os custos do tratamento da PAC. Esses custos são principalmente causados por internações hospitalares desnecessárias (ou por internação desnecessariamente prolongada) em casos de pneumonia leve, assim como pela prescrição exagerada de antibióticos. As autoridades devem se esforçar para melhorar a adesão às diretrizes ...

ECTOPIC ACTH SECRETION WITH CONCOMITANT HYPERAMYLASEMIA IN A PATIENT WITH SMALL CELL LUNG CARCINOMA: CASE REPORT.

Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization.

The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer.

Lung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20 % of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal approaches are now the norm. An improved knowledge of the prognostic variables would assist in defining which patients were better candidates to receive these newer intensive therapies. This single-center retrospective study of 97 previously untreated and histologically proven SCLC patients analysed the circulating neuroendocrine markers chromogranin A (CGA), pro-gastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) in addition to the other more classical variables. Fifty patients had limited-stage disease and 47 had extensive disease. Sixty patients had an ECOG performance status (PS) of 0-1 and 37 had PS 2-4. Median survival for the whole study population was 13 months. Univariate analysis and univariate Cox regression modeling found a statistically significant association between survival and PS, disease stage, and CGA, ProGRP, and NSE levels. Age and sex were not prognostic. A shorter survival time was found in patients with a PS equal to or >2, extensive stage disease, a serum CGA level >56 ng/ml, a serum ProGRP level >58 pg/ml, and a serum NSE level >19 ng/ml. This study has found that there is a potential role for ProGRP, NSE, and CGA in both staging and prognosing survival in SCLC patients.

Risk factors for brain metastases in surgically staged IIIA non-small cell lung cancer patients treated with surgery, radiotherapy and chemotherapy.

INTRODUCTION/AIM: Lung cancer is a leading cause of mortality among patients with carcinomas. The aim of this study was to point out risk factors for brain metastases (BM) appearance in patients with IIIA (N2) stage of nonsmall cell lung cancer (NSCLC) treated with three-modal therapy. METHODS: We analyzed data obtained from 107 patients with IIIA (N2) stage of NSCLC treated surgically with neoadjuvant therapy. The frequency of brain metastases was examined regarding age, sex, histological type and the size of tumor, nodal status, the sequence of radiotherapy and chemotherapy application and the type of chemotherapy. RESULTS: Two and 3-year incidence rates of BM were 35% and 46%, respectively. Forty-six percent of the patients recurred in the brain as their first failure in the period of three years. Histologically, the patients with nonsquamous cell lung carcinoma had significantly higher frequency of metastases in the brain compared with the group of squamous cell lung carcinoma (46%:30%; p = 0.021). Examining treatment-related parameters, treatment with taxane-platinum containing regimens was associated with a lower risk of brain metastases, than platinum-etoposide chemotherapy regimens (31%:52%; p = 0.011). Preoperative radiotherapy, with or without postoperative treatment, showed lower rate of metastases in the brain compared with postoperative radiotherapy treatment only (33%:48%; p = 0.035). CONCLUSION: Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2). Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.

Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer.

CONTEXT: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis. METHODS: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified. RESULTS: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers. CONCLUSION: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin.

[The value of neuroendocrine markers for response to therapy and survival in patients with advanced non-small cell lung cancer].

INTRODUCTION: Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. OBJECTIVE: The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. METHODS: A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. RESULTS: NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p < 0.05). There was significant correlation between therapy response and the percentage of positive tumour cells with neuroendocrine differentiation (p < 0.05). The one-year and two-year follow-up survival period in patients with neuroendocrine expression was 64% (without expression 28%; p < 0.001) and 30% (p = 0.000). CONCLUSION: Tissue expression of neuroendocrine markers influences greatly a therapeutic response in patients with advanced stage of NSCLC. Better therapeutic response was recorded in patients with possitive expression of neuroendocrine markers and higher percentage of positive tumour cells. Median survival time is higher in patients in Ill or IV stage of NSCLC, when neuroendocrine markers are expressed.

[Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer].

BACKGROUND/AIM: As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC) improves, brain metastases (BM) still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. METHODS: Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. RESULTS: One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004) vs. stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02). Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03). On multivariate analysis, timing of chemotherapy (p < 0.05) and stage IIIA vs. IIIB (p < 0.01) remained statistically significant. CONCLUSION: Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

[Non allergic simple eosinophilic pneumonia--Löffler syndrome--a case report study].

INTRODUCTION: Löffler syndrome is an acute, pneumonia of unknown ethiology. This disease is not often associated with bronchial asthma. In its asymptomatic form, this disease is reversible, transient, self-limited with no requests for specific therapy regimen. In the symptomatic form, as well as during its progression, treatment with steroids is very effective. Furthermore, in both acute eosinophilic and idiopathic chronic eosinophilic form, this kind of therapy ensures survival. CASE REPORT: The case of a 53-year-old Caucasian woman was presented with 2-month history of low grade fever, shortness of breath, cough and reduced exercise tolerance. Although she had an allergic accident on insects in history, non allergy reactions as well as an obstructive disease with that kind of origin were not detected on admission. The diagnosis of simple eosinophilic pneumonia (SEP) (Löffler's syndrome) was confirmed by transbronchial biopsy and by sternal testing. The peripheral blood eosinophilia with pulmonary eosinophilic infiltrates on X ray chest radiography were observed during clinical examination. Biopsy specimen of the lung parenchym showed changes associated with Löffler's syndrome. The diagnosis was, also, confirmed according to the radiographic findings of unilateral migratory infiltrates consistent pneumonia. DISCUSSION: Churg Strauss syndrome (CSS) has to be considered in this differential diagnosis. Frequently, this disease has extrinsic bronchial asthma with eosinophilic pneumonia in history: asthma is often associated with allergic bronchopulmonary aspergillosis. In the reported case, treatment with steroids resulted in a marked clinical improvement compared to nonsteroid therapy.

[Influence of chemiotherapeutic protocol and neuroendocrine differentiation on metastatic non-small cell lung cancer treatment results].

BACKGROUND/AIM: In 40-50% of patients with non-small cell lung cancer (NSCLC) at the time of making a diagnosis, the disease is yet at IIIb and IV stage. Standard in the treatment of these patient is the application of systemic chemiotherapy based on CIS/Carboplatin preparations. The aim of this study was to determine the influence of two different chemiotherapeutic protocols and neuroendocrine differentiation on treatment response and survival in patients with metastatic NSCLC. METHODS: We examined 85 patients with metastatic NSCLC, of which 51 with stage IIIb, and 34 with stage IV of the disease. The histologic diagnosis of NSCLC was determined by tissue assays using hematoxylin eosin method. Neuroendocrine differentiation was determined by immunohistochemical analysis of neuron-specific enolase (NSE), chromogranin A, and synapthophysin expression using monoclonal mouse anti-human bodies (DAKO, Denmark). According to chemiotherapeutic protocol, the patients were randomly assigned into combined Taxol + Cisplatin group (Tax + Cis, n = 35), and Cyclophosphamide + Etoposide + Carboplatin group (CEP, n = 50). The treatment was conducted within 4-6 chemiotherapeutic cycles. The efficacy was assessed after the therapy regimen and median survival time was assessed after the randomization. RESULTS: A total of 31 (36.47%) patients had a favourable therapeutic response, both partial and complete response (54.2% in the Tax + Cis group and 24% in CEP group of patients, respectively, p < 0.001). The median survival time in both groups was 13.1 months (15.3 months in the Tax + Cis group and 10.6 months in the CEP group, respectively, p < 0.001). A one-year follow-up survival period was confirmed in 40% of patients (60% only in the Tax + Cis group). A total of 23 (27.05%) patients with metastatic NSCLC had neuroendocrine differentiation. The disease progression or stable disease was noted only in patient with NSCLC without neuroendocrine differentiation (n = 42, 67.7%, p < 0.001). The median survival time in patients with NSCLC and neuroendocrine differentiation was 14.8 months, without neuroendocrine differentiation 10.7 months (p < 0.001). The patients with NSCLC and neuroendocrine differentiation in the CEP group had a longer one-year follow-up survival period than patients in Tax + Cis group (p < 0.001). In Tax-Cis group of patients, there was no significant difference in one-year follow-up survival period with neuroendocrine differentiation. CONCLUSION: Better therapeutic response and longer median survival time in metastatic NSCLC was obtained using Tax + Cis as compared to CEP protocol. Similar effect was noted using CEP protocol in patients with NSCLC and neuroendocrine differentiation.

[Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer].

BACKGROUND/AIM: Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC) neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: A clinical trial included 158 patients (74% males and 26% females), with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion) or chemotherapy only in stage III (with pleural effusion) and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. RESULTS: A total of 53 patients (34%) had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively). Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.50/0), 34 (21.5%) and 33 (20.1%) patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (< 0.001); a two-year survival time noted in 30% of the patients (p = 0.000). One year follow-up survival time was longer in the patients with neuron specific enolase and chromogranin A expression lung cancer (p < 0.001). Synapthophysin expression was not statisticaly significant for survival (p > 0.05). CONCLUSION: The results of this study suggest that almost the third of the advanced NSCLC has neuroendocrine differentiation. The median survival time of the treated patients is longer when the tumor is associated with neuron specific enolase and chromogranin A expression.