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ΕισαγωγήΤο bevacizumab και το erlotinib έχει αποδειχθεί ότι παρατείνουν τη συνολική επιβίωση σε ασθενείς με μη - πλακώδες μη μικροκυτταρικό καρκίνο του πνεύμονα ( NSCLC) . Σκοπός αυτής της μελέτης είναι να αξιολογηθεί η αποτελεσματικότητα και η τοξικότητα του συνδυασμού docetaxel , carboplatin ,bevacizumab και erlotinib στη θεραπεία πρώτης γραμμής ασθενών με NSCLC.ΜέθοδοιΣυνολικά 229 ασθενείς σταδίου ΙΙΙβ / IV μη πλακώδους NSCLC υποβλήθηκαν αρχικά σε δύο κύκλους χημειοθεραπείας με carboplatin 5.5AUC-docetaxel 100 mg/m2. Μετά την ολοκλήρωση των δύο κύκλων θεραπείας, οι ασθενείς αξιολογήθηκαν ως προς την ανταπόκριση και χωρίστηκαν σε τέσσερις ομάδες: 61/229 συνέχισαν με τέσσερις κύκλους χημειοθεραπείας (ομάδα ελέγχου) , 52/229 έλαβαν χημειοθεραπεία μαζι με erlotinib 150 mg ημερησίως, 56/229 έλαβαν χημειοθεραπεία συν bevacizumab 7,5 mg / kg , και 60/229 υποβλήθηκαν σε αγωγή με συνδυασμό χημειοθεραπείας , erlotinib και bevacizumab μέχρι την εξέλιξη της νόσου. Πρωταρχικός στόχος της μελέτης ήταν η συνολική επιβίωση .ΑποτελέσματαΣτα 4 χρόνια παρακολούθησης της μελέτης, δεν υπήρχε στατιστικά σημαντική διαφορά στην επιβίωση και στο χρόνο μέχρι την εξέλιξη της νόσου μεταξύ των τεσσάρων ομάδων θεραπείας . Μετά από δύο κύκλους χημειοθεραπείας , οι ασθενείς χωρίστηκαν ανάλογα με την απόκριση τους σε αυτούς που ανταποκρίθηκαν και σε αυτούς που δεν ανταποκρίθηκαν, προκειμένου να εξεταστεί ο ρόλος της αρχικής απόκρισης, ως ένας ανεξάρτητος παράγοντας στην επιβίωση. Οι ασθενείς που δεν απάντησαν και οι οποίοι έλαβαν συμπληρωματική θεραπεία με bevacizumab ή θεραπεία συνδυασμού είχαν ένα όφελος επιβίωσης 657 ημέρες (95 % CI 349 - 970 ) και 681 ημέρες ( 95 % CI 315 - 912 ) , αντίστοιχα , η οποία ήταν στατιστικά σημαντική σε σύγκριση με τη συνέχιση μόνο με κυτταροτοξική χημειοθεραπεία (Ρ < 0,001 ) . Η θεραπεία συνδυασμού είχε ένα προφίλ ασφάλειας συγκρίσιμο με αυτό του bevacizumab και του erlotinib λαμβανόμενα ξεχωριστά .ΣυμπέρασμαΗ χορήγηση bevacizumab-erlotinib σε συνδυασμό με χημειοθεραπεία πρώτης γραμμής , που ακολουθείται από μονοθεραπεία με bevacizumab και erlotinib ως θεραπεία συντήρησης έδειξε ελπιδοφόρα αποτελέσματα σε ασθενείς με ΜΜΚΠ , με μειωμένη τοξικότητα σε σύγκριση με τη χημειοθεραπεία μόνο , αλλά δεν μεταφράζεται σε μεγαλύτερη συνολική επιβίωση.

Background:Νeuroendocrine tumors of the lungs are rare arising in the thymus and gastro-entero-pancreatic tract and belonging to foregut of neuroendocrine tumors. The aim of the present prospective study was to estimate the potential impact of single-photon emission computed tomography somatostatin receptor scintigraphy using 99mTc-Tektrotyd on diagnosis, treatment response, and prognosis in patients with neuroendocrine tumors of the lungs.Methods:Thirty-six patients with neuroendocrine tumors of the lungs were evaluated by using 99mTc-HYNIC-TOC scintigraphy. The scintigraphic results were compared to liver tissue uptake (Krenning score). Likewise, the functional imaging results were compared with biochemical indices including chromogranin A, neuroendocrine-specific enolase, and insulin-like growth factor 1 at the time of diagnosis (baseline) and disease progression.Results:The number of somatostatin receptors, expressed with Krenning score, did not show any correlation with the survival of patients both at baseline ( P = .08) and at disease progression ( P = .24), and scintigraphy results did not relate significantly to progression-free survival. Comparing the results of 99mTc-HYNIC-TOC scintigraphy according to the response of patients in the initial treatment, a statistically significant negative correlation was observed both in the first and in the second scintigraphy with patients’ response ( P = .001 and P < .001, respectively). The concentrations of biochemical markers were in accordance with scintigraphy results in the diagnosis.Conclusion:This study indicates that 99mTc-HYNIC-TOC scintigraphy appears to be a reliable, noninvasive technique for detection of primary neuroendocrine tumors and their locoregional or distant metastases, although it cannot be used as a neuroendocrine tumors of the lungs predictive technique.

Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients. Methods: We prospectively studied 26 NSCLC patients that received immunotherapy (either pembrolizumab or nivolumab). IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 were analyzed by flow cytometry at the time of diagnosis and at 3 months after initiation of anti-PD-1 inhibition. Results: Increased cytokine values (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6 and IL-8) at the time of diagnosis and at 3 months after initiation of treatment were significantly correlated with improved response to immunotherapy and prolonged OS. There was no correlation between cytokine levels and programmed cell death ligand-1 (PD-L1) expression. Conclusions: Increased IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 levels resulted in better response to NSCLC anti-PD-1 inhibition and longer survival, and this could potentially play an important role in selecting patients that would benefit from anti-PD-1 inhibitors.

Background: Nivolumab has been approved as 2nd line treatment of patients with advanced NSCLC regardless of tumor PD-L1 expression. Aim: To evaluate the efficacy and safety of nivolumab among NSCLC patients treated in a single center after 1 year of clinical practice Methods: The medical files of 48 patients (43 males) who received ≥1 dose of nivolubab were retrospectively (time period: 29/2/2016-10/2/2017). Results: The mean age of the study population was 64.9 ±8.5 years, all patients had stage IIIB-IV while the histological types were: squamous cell carcinoma (22), adenocarcinoma (22), NSCC NOS (3), large cell neuroendocrine carcinoma (1). The number of previous lines of platinum based chemotherapy was: one for 22 patients, two for 18 and the rest had received ≥3 lines. All patients received nivolumab as monotherapy (3 mg/kg/2 weeks IV). The median number of doses was 5 (min:1, max:23). 16 patients had received ≤4 doses and response could not be evaluated (all had stable disease based on chest X-ray). Two patients had partial response (PR, RECIST criteria) and 3 presented with improvement but less than PR. 13 patients had stable disease and 12 had progressive disease or unacceptable toxicity after a median of 6 doses (min:3, max:15). Two patients died after receiving 1 dose of the drug (no death was attributed to nivolumab). Four patients (8%) presented with serious treatment-related adverse events (1: pericardial/pleural effusions, 1: interstitial pneumonitis, 1: colitis/bowel perforation and 1: severe generalized edema). Conclusion: Nivolumab demonstrated clinically meaningful activity and satisfactory safety profile as 2nd line treatment for patients with advanced NSCLC.

Background: Several preclinical and clinical studies have demonstrated that cyclooxygenase-2 (Cox-2) inhibitors have anti-tumor activity in the treatment of non-small-cell lung cancer. However, there is little data on the use of Cox2 inhibitors in patients with small cell carcinoma (SCLC). The aim of this prospective study was to evaluate the role of Rofecoxib , a selective Cox2 inhibitor in combination with conventional chemotherapy in SCLC treatment. Methods: Patients with extensive small-cell lung cancer and median age 62±11.7 years, were randomized to receive oral rofecoxib 12.5 mg twice daily every day plus cisplatin 25 mg/m(2) and etoposide 100 mg/m2 or chemotherapy alone. Both regimens were repeated every 4 weeks until disease progression. Primary end points of our study were survival and time to progression Results: 98 patients were enrolled. 44 pts were randomly assigned chemotherapy plus rofecoxib and 54 chemotherapy alone. Median OS was 14 months (95% CI, 11.5 to 16 mo) for the cox-2 arm and 7.7 months (95% CI, 6 to 9.4) for chemotherapy(control) arm, which is statistically significant (p= 0.001). Median time to progression was 9.2 months (95% CI, 7.4 to 11) for the cox-2 arm and 5 months (95% CI, 3.7 to 6.5) for the control arm (p= 0.004). The response rates were 48.0 and 29.6%, respectively. Toxicity was mild, and no increase in cardiovascular events was observed. Conclusion: In advanced SCLC, rofecoxib in combination with chemotherapy improves survival , but the results must be interpreted with caution due to the limited number of patients.

Aims and Objectives: The aim of this study was to evaluate the comorbidity of diadetes mellitus(D.M) and to examine the survival difference between the patients with NSCLC, with history of D.M. and those without. Methods: 1222 patients first diagnosed with NSCLC, with non-operable stage IIIa, IIIb and IV, received 1st line platinum based chemotherapy (CHT) for up to six cycles. 321/1222 patients suffered from D.M. 301/1222 who presented progression of disease they submitted in 2nd line by which 69/301 were diabetic. 74 who progressed after the completion of 2nd line CHT were treated with 3nd line CHT by which 19/74 had history of D.M. Results: The patients without D.M. had longer time to progression (TTP), than those without, statistically important (p

Konstantinos Zarogoulidis,1 Efimia Boutsikou,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Lutz Freitag,2 Konstantinos Porpodis,1 Dimitrios Latsios,1 Theodoros Kontakiotis,1 Haidong Huang,3,4 Qiang Li,4 Wolfgang Hohenforst-Schmidt,5 Maria Kipourou,1 J Francis Turner,6 Dionysios Spyratos11Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 3Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, Detroit, MI, USA; 4Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 5II Medical Clinic, “Coburg” Regional Hospital, University of Wuerzburg, Coburg, Germany; 6Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, NV, USABackground: To evaluate the benefit of second-line chemotherapy with platinum-based treatment in patients with recurrent small cell lung cancer (SCLC).Patients and methods: A total of 535 patients continued with follow-up or best supportive care if needed, and 229 patients who progressed after the completion of first-line chemotherapy were treated with second-line chemotherapy at the time of progression. In total, 103/229 patients received paclitaxel 190 mg/m2 and carboplatin 5.5 area under the curve while 126/229 patients received etoposide 200 mg/m2 and carboplatin 5.5 area under the curve every 28 days.Results: Patients administered second-line chemotherapy lived significantly longer, with a median survival of 422 days compared to 228 days in patients with best supportive care alone (P

Konstantinos Zarogoulidis,1 Eftimios Ziogas,1 Efimia Boutsikou,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Theodoros Kontakiotis,1 Kosmas Tsakiridis,3 Konstantinos Porpodis,1 Dimitrios Latsios,1 Olga Chatzizisi,4 Ilias Karapantzos,5 Qiang Li,6 Georgios Kyriazis21Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 3Thoracic Surgery Department, "Saint Luke" Private Hospital, Panorama, Thessaloniki, Greece; 4Immunology Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Ear, Nose and Throat Department, "Saint Luke" Private Hospital, Panorama, Thessaloniki, Greece; 6Respiratory Diseases Department, Shanghai hospital, Second Military Medical University, Shanghai, People's Republic of ChinaPurpose: To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.Patients and methods: Patients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m2 intravenously on day 1, ifosfamide 3.5 mg/m2 intravenously on day 1, and etoposide 200 mg/m2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.Results: Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B (P < 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P < 0.05).Conclusion: Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.Keywords: interferon, SCLC, lung cancer, immunomodifiers

Konstantinos Zarogoulidis,1 Dimitrios Latsios,1 Konstantinos Porpodis,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Nick Antoniou,1 Wolfgang Hohenforst-Schmidt,3 Ellada Eleftheriadou,1 Efimia Boutsikou,1 Theodoros Kontakiotis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2University Pulmonary Department- Interventional Unit, Ruhrlandklinik, University, University of Duisburg-Essen, Essen, Germany; 3II Medical Clinic, Hospital of Coburg, University of Wuerzburg, Coburg, GermanyBackground: Many patients with limited disease (LD) behave similarly to those with extensive disease (ED) from a prognostic point of view. On the other hand, a proportion of patients with ED small-cell lung cancer (SCLC) behave similarly to those with LD.Patients and methods: In this retrospective study analysis, 764 patients with proven SCLC were included and managed with the same therapeutic protocols. Of these patients, 278 (36.4%) had LD, while 486 (63.6%) had ED.Results: No statistically significant difference was observed for survival for IA and IB disease stages (P = 0.254) and between IIA and IIB stages (P = 0.256) according to the new tumor, node, metastasis (TNM) staging classification classification. In addition, no statistical significant difference was observed for survival between patients with (IIA + IIB) and IIIA (P = 0.951), (IIA + IIIA, P = 0.658), and (IIB + IIIA, P = 0.573) stages. Statistical significant difference was observed for survival among the LD SCLC patients with (IA + IB), (IIA + IIB + IIIA), and IIIB stages (P < 0.001). Similarly, statistical significance was observed for ED SCLC patients with (IIA + IIB + IIIA), IIIB, and IV stages (P < 0.001).Conclusions: Although stratification of SCLC patients in LD and ED is generally satisfactory, the TNM staging system is recommended for more detailed prognostic information and treatment evaluation in these patients.Keywords: small-cell lung cancer, staging, lung cancer