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Background/aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed., Patients and Methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting., Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment., Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Real-world evidence regarding the prevalence of epidermal growth factor receptor (EGFR) mutation-positive status (M+) and the clinicopathological characteristics associated with the presence of EGFR mutations in advanced non-small cell lung cancer (NSCLC) is scarce, especially among Caucasian populations. The present study aimed to bridge this gap, as well as to record treatment patterns and outcomes in routine-care settings., Patients and Methods: REASON (NCT01153399) was a prospective study of patients with stage IIIB/IV NSCLC and known EGFR mutation status. Clinicopathological, treatment characteristics and clinical outcomes were recorded and correlated with EGFR mutation testing results., Results: Of 575 enrolled patients, EGFR mutations were detected in 15.7% of them. Male gender (p=0.008) and smoking (p<0.001), but not adenocarcinoma, were associated with EGFR M+ status. In the EGFR M+ subpopulation (n=88), absence of bone and/or brain metastasis and presence of exon 19 EGFR M+ status at diagnosis were independently associated with longer progression-free survival (PFS) (p=0.011 and p=0.040, respectively)., Conclusion: In our population, males and smokers had decreased odds of harboring an EGFR mutation, while adenocarcinoma histology was not a significant predictor of EGFR M+ status. EGFR M+ patients with bone and/or brain metastases at diagnosis or mutations other than exon 19 deletions were at increased risk for earlier disease progression., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To investigate the effect of serum from patients with non-small cell lung cancer (NSCLC) on in vitro cytotoxicity of the clonal cell line NK-92., Materials and Methods: Twenty-six patients with NSCLC were included in this study. NK-92 cells were incubated in medium supplemented with 25% of each patient's serum (before and after chemotherapy) for 24 h, then washed and tested for cytotoxicity against NK-sensitive K562 targets., Results: The cytotoxicity of NK-92 cells exposed to serum from patients with NSCLC before chemotherapy initiation was significantly reduced compared to that upon incubated with serum from healthy individuals (p<0.001). NK-92 cytotoxicity was further reduced upon exposure to patient's serum after the first and third chemo therapy cycles (p<0.001)., Conclusion: The results of our in vitro study suggest that serum of patients with NSCLC may exert per se an inhibitory effect on the cytotoxicity of NK-92 cells and this negative regulation may be enhanced with chemotherapy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To further evaluate the prognostic significance of pre-treatment serum and pleural fluid levels of vascular endothelial growth factor VEGF in patients with non-small cell lung cancer (NSCLC) presenting with malignant pleural effusion (MPE)., Patients and Methods: Forty consecutive newly-diagnosed patients with NSCLC with MPE at presentation but without distant metastases were prospectively enrolled. The prognostic value of serum and pleural fluid VEGF levels for overall survival (OS) and progression-free survival (PFS) was assessed by Cox regression analysis., Results: The median serum VEGF level was significantly higher in patients compared to healthy controls (p<0.001). Serum VEGF higher than 375 pg/ml, pleural fluid VEGF greater than the median value and the presence of progressive disease were all significantly associated with reduced OS and PFS, both in univariate and multivariate analyses., Conclusion: The results of our study suggest that increased pre-treatment serum and pleural fluid levels of VEGF may be independent predictors of a worse survival in patients with advanced-stage NSCLC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To determine the more effective dosing sequence of intermittent erlotinib and docetaxel for treating chemotherapy-naive patients with advanced Non-Small Cell Lung Cancer (NSCLC)., Patients and Methods: Patients were randomized to receive daily erlotinib for 12 consecutive days prior to docetaxel (Arm A) or after docetaxel (Arm B). Progression-free survival (PFS) was the primary end-point; secondary end-points were overall survival (OS) and objective response rate (ORR)., Results: Fifty eligible patients received a total of 226 treatment cycles (median: 3). Median PFS and OS were 3.6 months and 10.5 months, respectively (differences were not statistically significant between the two arms). Neutropenia grade 3 and 4 occurred in 15 patients, while two patients developed grade 3 diarrhea. There were two treatment-related deaths (pulmonary embolism and non-neutropenic sepsis)., Conclusion: Intermittent administration of erlotinib does not appear to improve the clinical outcome of single-agent docetaxel chemotherapy in unselected patients with NSCLC in the first-line setting., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The aim of the study was to evaluate the exhaled breath condensate (EBC) levels of a valid oxidative stress marker, 8-isoprostane, before and after chemotherapy, in patients with non small cell lung cancer (NSCLC) in correlation with the extent of the disease and response to treatment., Patients and Methods: Forty-five patients with inoperable NSCLC were initially enrolled in the study. Twenty-nine of them were finally evaluated in regards to 8-isoprostane levels in EBC before and after chemotherapy., Results: 8-Isoprostane levels were significantly lower after chemotherapy (p=0.014). Further analysis showed that the differences were mainly attributed: a) to the extent of the disease, with patients diagnosed with up to locally advanced disease (stages IB-IIIB) having significantly lower EBC 8-isoprostane levels post-chemotherapy (p=0.031); and b) to the response to treatment, with patients evaluated with partial response to treatment having significantly lower EBC 8-isoprostane levels post-chemotherapy (p=0.02)., Conclusion: In this prospective study, we showed that 8-isoprostane might represent a biomarker in NSCLC, reflecting both response to chemotherapy, as well as the extent of the disease., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The intercellular cell-adhesion molecule-1 (ICAM-1) is a transmembrane molecule and a distinguished member of the Immunoglobulin superfamily of proteins that participates in many important processes, including leukocyte endothelial transmigration, cell signaling, cell-cell interaction, cell polarity and tissue stability. ICAM-1and its soluble part are highly expressed in inflammatory conditions, chronic diseases and a number of malignancies. In the present article we present the implications of ICAM-1 in the progression and prognosis of one of the major global killers of our era: lung cancer., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Invasive staging of mediastinal lymph nodes is recommended for the majority of patients with potentially resectable non-small cell lung cancer. In the past, 'blind' transbronchial needle aspiration during bronchoscopy and mediastinoscopy, a surgical procedure conducted under general anesthesia, were the only diagnostic methods. The latter is still considered the 'gold standard'; however, two novel, minimally-invasive techniques have emerged for the evaluation of the mediastinum: endoscopic (transesophageal) and endobronchial ultrasound--both performed using a dedicated echoendoscope, facilitating the ultrasound-guided, real-time aspiration of mediastinal lymph nodes. These methods are well-tolerated under local anesthesia and moderate sedation, with very low complication rates. Current guidelines on the invasive mediastinal staging of lung cancer still state that a negative needle aspiration result from these methods should be confirmed by mediastinoscopy. As more experience is gathered and echoendoscopes evolve, a thorough endosonographic evaluation of the mediastinum by both techniques, will obviate the need for surgical staging in the vast majority of patients and reduce the number of futile thoracotomies.

Aim: The purpose of this study was to compare two single agents paclitaxel (intravenous) versus vinorelbine (oral) in non-small cell lung cancer (NSCLC) patients with performance status (PS):2., Patients and Methods: The patients were randomized to receive either oral vinorelbine 60 mg/m(2) on days 1, 8, 15 every 4 weeks for 4 cycles (group A) or paclitaxel 90 mg/m(2) intravenously for 1 h on days 1, 8, 15 every 4 weeks for a total of 4 cycles (group B)., Results: Among the 74 eligible patients (36 in arm A and 38 in arm B) in arm A, two (6%) had a partial response (95% CI, 0.7-18.7) and 5 (14%) had stable disease (95% CI, 4.7-29.5). In arm B, five (13%) had a partial response (95% CI, 4.4-28.1) and 7 (18%) had stable disease (95% CI, 7.7-34.3). No significant difference was found in terms of clinical benefit between the two groups after two cycles of treatment except for appetite in favour of paclitaxel (p=0.01). Median survival was 3.1 months (95% CI, 2.2-4.0) for arm A and 5.1 months (95% CI, 2.7-7.6) for arm B (p=0.95). Toxicity was mild and only alopecia was more profound in the patients of arm B (p=0.008)., Conclusion: No significant difference was found in clinical benefit between PS:2 NSCLC patients treated with either vinorelbine or paclitaxel.

Zoledronic acid (Zometa, Novartis, Basel, Switzerland) is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases. The safety and efficacy of intravenous zoledronic acid in lung cancer patients was assessed. In 86 patients with newly diagnosed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) and bone metastases, 4 mg of zoledronic acid was administered with rapid 15-minute intravenous infusion every 3-4 weeks. A total of 414 infusions were administered over a 24-month period during which a statistically significant decrease in serum calcium levels (p = 0.03) was observed. Serum alkaline phosphatase (ALP) also decreased but not significantly. With regard to clinical efficacy, 55 of our patients stabilized or reduced their need for analgesic treatment. No significant side-effects, including fever, hemodynamic instability and renal dysfunction, were seen. We conclude that the rapid infusion of zoledronic acid is safe and convenient for lung cancer patients even after the 3rd and 6th months follow-up.

Background: The aim of this study was to determine the overall survival, progression-free survival, and toxicity associated with adjuvant administration of docetaxel and gemcitabine for completely resected patients with stage II and IIIA non-small cell lung cancer (NSCLC)., Patients and Methods: Thirty-nine eligible patients had surgical resection for pathological stage II or IIIA disease and received postoperative gemcitabine 1000 mg/m2 followed by docetaxel 80 mg/m2 on days 1 and 14. Cycles were repeated every 28 days., Results: Treatment compliance was acceptable, at 83%. The median duration of follow-up, time to disease progression, and overall survival was 36.7 months, 17 months and 21 months, respectively. Toxicities were acceptable. Treatment failure revealed brain metastasis (15%), intrathoracic recurrence (24%) and systemic metastasis (36%)., Conclusion: The biweekly administration of docetaxel and gemcitabine is a safe, well-tolerated and convenient chemotherapy regimen in the adjuvant setting of completely resected NSCLC stage II and III, with efficacy similar to that reported in other regimens. Hence, this nonplatinum based regimen appears promising and warrants further evaluation.

Background: The high prevalence of bone metastases in stage IV non-small cell lung cancer (NSCLC) patients contributes substantially to the burden of the disease by resulting in significant skeletal morbidity. Ibandronate is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases., Patients and Methods: In 32 patients with newly diagnosed NSCLC and bone metastases, 4 mg of ibandronate were administered, as a rapid 20-minute intravenous infusion every 3-4 weeks., Results: A total of 189 infusions were administered over a 24-month period, during which a statistically significant decrease in calcium serum levels (p=0.03) was observed. The serum levels of alkaline phosphatase (ALP) were also decreased, but not significantly. With regard to clinical efficacy, 24 of our patients stabilized or reduced their need for analgesic treatment. The reduced time of infusion (20 min vs. 2 h) did not correlate with any side-effects, including vital sign deterioration and renal dysfunction., Conclusion: The rapid infusion of ibandronate in lung cancer patients with bone metastases is a safe and convenient procedure that may be administered in a day-clinic setting.

With the significant increase of the average lifespan in the industrial world, the number of elderly people, as a proportion of the total population, has risen dramatically. It has been estimated that this trend will accelerate and that, by the year 2020, the number of people aged >80 years will soar by 135%. With age being the greatest risk factor for prostate cancer, this disease has understandably become one of the greatest public health concerns. Recently, considerable attention has been focused on prostate cancer management in the elderly, with specific emphasis on the question of whether, or not, it should differ from that of younger patients. We thoroughly reviewed the existing evidence on screening, diagnosis and treatment of prostate cancer in the elderly and concluded that age alone should not constitute an obstruction for optimal treatment administration. Physicians treating aged prostate cancer patients should be trained in an individualized approach, based on clinical performance status and comorbitities.

Background: The standard treatment for advanced non-small cell lung cancer (NSCLC) currently consists of platinum-based, combination chemotherapy of limited efficacy and possible toxicity. The bi-weekly administration of docetaxel and gemcitabine for advanced NSCLC was evaluated in a phase II study (objective response rate, median survival, median duration of response and safety)., Patients and Methods: A total of 170 cycles were administered to 31 patients with advanced NSCLC and a median age of 66 years (range 47-75 years). Patients received docetaxel 80 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 14 of a 28-day cycle., Results: Sixteen patients achieved a PR (16/31, 55.2%), 3 patients had SD (3/31, 10.3%) and 10 (10/31, 34.5%) had PD. The median time to disease progression was 3 months (range 0-12 months) with a mean survival of 10 months (range 3-31 months). Haematological and non-haematological toxic effects were generally mild to moderate and manageable: Grade 3 neurotoxicity and allergy occurred in 2 patients (6.4%) and 1 patient (3.2%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 24 patients (77.4%)., Conclusion: The bi-weekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of advanced NSCLC, with efficacy similar to that reported in other regimens.

This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin, supported by granulocyte colony-stimulating factor, as first-line chemotherapy in metastatic breast cancer. Patients received epirubicin (60 mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Prophylactic granulocyte colony-stimulating factor (5 micrograms/kg) was administered daily for 5 days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective responses occurred in 45 patients (65%; 95% confidence interval: 53-76%), with 11 (16%) complete responses and 34 (49%) partial responses. Responses were observed at all metastatic sites. The median response duration was 8 months (range 4-68), median time to progression was 10 months (range 4-68) and median overall survival was 24 months (range 7-68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left ventricular ejection, fraction measured in 50 patients, fell below normal in 14 patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but none developed congestive cardiac failure. The docetaxel-epirubicin regimen is extremely effective in poor prognosis breast cancer patients with visceral metastases, with significant overall and complete responses, followed by prolonged survival in responders. Although myelosuppression remains the major toxicity, prophylactic GCSF administration was associated with a small percentage of neutropenic fever.

Background: Both tissue c-erbB-2 expression and serum levels the shed protein have been shown to correlate with tumour stage in a range of adenocarcinomas. This study measured serum and urinary c-erbB-2 levels in patients with gastric cancer, assessing their role in cancer-specific survival and the effects of resectional surgery., Patients and Methods: Serum and urinary c-erbB-2 concentrations were measured with commercial enzyme-linked immunosorbent assay in 41 healthy controls and in 54 gastric cancer patients. Serum and urinary c-erbB-2 levels in cancer patients were determined before and 7 days following tumour surgery., Results: Preoperative serum and urinary c-erbB-2 levels in gastric cancer patients were significantly higher than those in controls although there were no significant associations between these levels and tumour pathology. Serum c-erbB-2 levels decreased significantly after radical resection of the primary tumour and were an independent prognostic factor for survival, whereas there were no changes in urinary c-erbB-2 levels after surgery or an association with patient survival., Conclusion: Gastric cancer patients show higher serum and urinary c-erbB-2 levels compared to healthy controls. Preoperative serum c-erbB-2 concentration decreases significantly after radical resection of the primary tumour and is an independent prognostic factor for patient survival.