111 results on '"Paris Kosmidis"'
Search Results
2. Abstract P1-12-01: Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial
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Flora Zagouri, Georgia-Angeliki Koliou, Foteinos Dimitrakopoulos, Christos Papadimitriou, Ioannis Binas, Angelos Koutras, Pavlos Papakostas, Christos Markopoulos, Vasileios Venizelos, Grigorios Xepapadakis, Charisios Karanikiotis, Amanda Psyrri, Dimitrios Bafaloukos, Paris Kosmidis, Gerasimos Aravantinos, Eleni Res, Davide Mauri, Anna Koumarianou, Kalliopi Petraki, Anna Tsipoura, Dimitrios Pectasides, Helen Gogas, and George Fountzilas
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Cancer Research ,Oncology - Abstract
Background: Dose-dense sequential chemotherapy based on anthracyclines and taxanes has achieved an 18% reduction of recurrence risk in the adjuvant setting of early breast cancer (BC). However, the optimal chemotherapy schedule and the preferable interval between cycles are still under investigation. Methods: A total of 990 eligible BC patients were randomized to receive either 3 cycles of epirubicin (E,110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by 3 cycles of intensified CMF (Control Arm A, E-T-CMF; 333 patients) or three cycles of epirubicin followed by 3 cycles of CMF followed by 9 consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Experimental Arm B, E-CMF-wD; 331) or 9 consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Experimental Arm C, E-CMF-wT; 326). Trastuzumab was administered for HER2-positive disease. The primary endpoint was disease-free survival (DFS). Results: At a median follow-up of 13.3 years, 330 DFS events (33.3%) had been reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus control arm A either in the entire cohort (HR=0.90, p=0.38 and HR=0.85, p=0.20) or among HER2-positive, trastuzumab-treated patients (HR=0.69, p=0.13 and HR=0.67, p=0.13). Thirty-four patients (3.4%) developed secondary neoplasms. Conclusions: Overall, no significant differences in DFS or OS were found amongst the studied regimens after a long-term observational period. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033 Citation Format: Flora Zagouri, Georgia-Angeliki Koliou, Foteinos Dimitrakopoulos, Christos Papadimitriou, Ioannis Binas, Angelos Koutras, Pavlos Papakostas, Christos Markopoulos, Vasileios Venizelos, Grigorios Xepapadakis, Charisios Karanikiotis, Amanda Psyrri, Dimitrios Bafaloukos, Paris Kosmidis, Gerasimos Aravantinos, Eleni Res, Davide Mauri, Anna Koumarianou, Kalliopi Petraki, Anna Tsipoura, Dimitrios Pectasides, Helen Gogas, George Fountzilas. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-01.
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- 2022
3. Artificial intelligence supporting cancer patients across Europe-The ASCAPE project
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Lazaros Tzelves, Ioannis Manolitsis, Ioannis Varkarakis, Mirjana Ivanovic, Miltiadis Kokkonidis, Cristina Sabater Useros, Thanos Kosmidis, Montserrat Muñoz, Imma Grau, Manos Athanatos, Anamaria Vizitiu, Konstantinos Lampropoulos, Tzortzia Koutsouri, Dimitra Stefanatou, Konstantinos Perrakis, Christina Stratigaki, Serge Autexier, Paris Kosmidis, and Antonis Valachis
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Male ,Physician-Patient Relations ,Multidisciplinary ,Artificial Intelligence ,Quality of Life ,Humans ,Prostatic Neoplasms ,Breast Neoplasms ,Female ,Longitudinal Studies - Abstract
Introduction Breast and prostate cancer survivors can experience impaired quality of life (QoL) in several QoL domains. The current strategy to support cancer survivors with impaired QoL is suboptimal, leading to unmet patient needs. ASCAPE aims to provide personalized- and artificial intelligence (AI)-based predictions for QoL issues in breast- and prostate cancer patients as well as to suggest potential interventions to their physicians to offer a more modern and holistic approach on cancer rehabilitation. Methods and analyses An AI-based platform aiming to predict QoL issues and suggest appropriate interventions to clinicians will be built based on patient data gathered through medical records, questionnaires, apps, and wearables. This platform will be prospectively evaluated through a longitudinal study where breast and prostate cancer survivors from four different study sites across the Europe will be enrolled. The evaluation of the AI-based follow-up strategy through the ASCAPE platform will be based on patients’ experience, engagement, and potential improvement in QoL during the study as well as on clinicians’ view on how ASCAPE platform impacts their clinical practice and doctor-patient relationship, and their experience in using the platform. Ethics and dissemination ASCAPE is the first research project that will prospectively investigate an AI-based approach for an individualized follow-up strategy for patients with breast- or prostate cancer focusing on patients’ QoL issues. ASCAPE represents a paradigm shift both in terms of a more individualized approach for follow-up based on QoL issues, which is an unmet need for cancer survivors, and in terms of how to use Big Data in cancer care through democratizing the knowledge and the access to AI and Big Data related innovations. Trial registration Trial Registration on clinicaltrials.gov: NCT04879563.
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- 2022
4. Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab
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Domenico Galetta, Giuseppe Lo Russo, Beatriz Jimenez, Alessio Gili, Panagiotis Baxevanos, Helena Linardou, Alessandro De Toma, Paris Kosmidis, Ana Collazo-Lorduy, Diego Signorelli, Marco Banini, Marina Chiara Garassino, Andrea Camerini, Alex Friedlaender, Alfredo Addeo, Antonio Calles, Giuseppe Luigi Banna, Panagiota Economopoulou, A. Christopoulou, Giulio Metro, Fausto Roila, and Giannis Mountzios
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,B7-H1 Antigen ,030218 nuclear medicine & medical imaging ,Young Adult ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,PD-L1 ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Lung ,Aged ,Retrospective Studies ,Aged, 80 and over ,Performance status ,biology ,business.industry ,digestive, oral, and skin physiology ,Front line ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Progression-Free Survival ,humanities ,respiratory tract diseases ,Europe ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Non small cell ,business - Abstract
Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcom...
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- 2020
5. Impact of Bevacizumab Versus Erlotinib on Tumor Metrics in Patients With Previously Untreated Advanced Non-small Cell Lung Cancer: A Study by the Hellenic Cooperative Oncology Group
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Helena Linardou, Giannis Mountzios, Paris Kosmidis, Georgia-Angeliki Koliou, Aphrodite Charitandi, Epaminontas Samantas, George Fountzilas, Xanthippi Mavropoulou, and Anna Kalogera-Fountzila
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Bevacizumab ,business.industry ,medicine.medical_treatment ,General Medicine ,medicine.disease ,Tumor response ,respiratory tract diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,Medicine ,In patient ,Erlotinib ,Non small cell ,business ,Lung cancer ,neoplasms ,medicine.drug - Abstract
Background The mechanism of action of bevacizumab and erlotinib is quite different in the treatment of advanced non-small cell lung cancer (NSCLC). This study sought to compare the two targeted therapies in terms of sequential tumor response metrics. Patients and methods Parameters of radiological tumor response evaluation were assessed at baseline and periodically in 58 patients receiving either bevacizumab plus platinum-based chemotherapy (N=25) or erlotinib (N=33). Results Bevacizumab-treated patients had lower longest diameter at best response compared to the erlotinib group (p=0.011). The longest diameter, tumor volume and density significantly decreased from baseline to best response for the entire cohort and bevacizumab-treated patients; no difference was found in the erlotinib group. Conclusion Treatment with bevacizumab substantially improved tumor metrics between baseline and each cycle of treatment, as well as between baseline and best response, in patients with advanced NSCLC.
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- 2020
6. Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma
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George Fountzilas, Elizabeth Psoma, Paris Kosmidis, Foteinos-Ioannis Dimitrakopoulos, Kyriaki Papadopoulou, Dimitra Rontogianni, Georgia-Angeliki Koliou, Anastasios Visvikis, Anna Kalogera-Fountzila, Jannis Constantinidis, and Mattheos Bobos
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endocrine system ,Cancer Research ,Endothelin receptor type A ,business.industry ,Single-nucleotide polymorphism ,General Medicine ,medicine.disease ,Nibrin ,Andrology ,03 medical and health sciences ,Vascular endothelial growth factor A ,0302 clinical medicine ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Genotype ,Medicine ,Clinical significance ,business ,Pterygoid Muscles - Abstract
BACKGROUND/AIM The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA -1154 G/A (rs1570360), -2578 A/C (rs699947), -1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS -671 A/G (rs1800682) was performed by using Sanger sequencing. RESULTS The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA -2578, VEGFA -1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA -2578 CC as compared to AC (HR=0.24, p=0.060). CONCLUSION The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group.
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- 2020
7. Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry
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Giannis Mountzios, David Planchard, Giulio Metro, Dora Tsiouda, Arsela Prelaj, Sofia Lampaki, Walid Shalata, Mariona Riudavets, Petros Christopoulos, Nicolas Girard, Víctor Albarrán-Artahona, Rosario Garcia Campelo, Konstantinos Samitas, Giuseppe Luigi Banna, Ioannis Boukovinas, Abed Agbarya, Anna Koumarianou, Eleni-Isidora Perdikouri, Paris Kosmidis, Helena Linardou, David Mauri, Dimitrios Mavroudis, Ilias Athanasiadis, Haralambos Kalofonos, Nikolaos Xenidis, Ippokratis Korantzis, Alexandros Ardavanis, Grigorios Rallis, Achille Bottiglieri, Konstantinos Efthymiadis, Georgios Oikonomopoulos, Alexandros Kokkalis, Emmanouil Saloustros, Nikolaos Tsoukalas, Dimitra Bartzi, Panagiota Economopoulou, Amanda Psyrri, Martin Reck, and Giuseppe Lo Russo
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Pulmonary and Respiratory Medicine ,Oncology - Published
- 2023
8. Recurrence-free Survival and Safety of Imatinib in Patients With Gastrointestinal Stromal Tumour (GIST) in Greece
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Athanasios Kotsakis, Christos N. Papandreou, Ioannis Boukovinas, Vasiliki Michalaki, Christos Christodoulou, Vasiliki Sidiropoulou, Gerasimos Aravantinos, Antonios Avgerinos, Paris Kosmidis, Nikolaos Androulakis, and Olga Kousidou
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,Gastrointestinal Stromal Tumors ,medicine.medical_treatment ,DNA Mutational Analysis ,Kaplan-Meier Estimate ,Disease-Free Survival ,Recurrence free survival ,Internal medicine ,medicine ,Humans ,In patient ,Time to treatment failure ,Univariate analysis ,Greece ,GiST ,business.industry ,Imatinib ,General Medicine ,Middle Aged ,Treatment Outcome ,Imatinib Mesylate ,Female ,Neoplasm Recurrence, Local ,business ,Adjuvant ,medicine.drug - Abstract
AIM The purpose of the Imadje study was to confirm the efficacy and safety of imatinib, following resection of kit-positive gastrointestinal stromal tumour (GIST), in the adjuvant setting in the Greek population. PATIENTS AND METHODS A total of 34 adult patients already receiving imatinib were enrolled. Recurrence-free (RFS) and overall survival, as well as time to treatment failure and safety were assessed. RESULTS Overall survival could not be estimated in the present study, as no death occurred. Overall, 91.2% of patients were recurrence-free at 36 months, while the median time to treatment failure was 35 months. No new or unexpected safety findings were observed. Mutation analysis in 14 patients showed that the most frequent mutations were located in KIT exon 11 (64.3%) and exon 9 (28.6%). Univariate analysis showed that only surgical resection with a margin classification of R0 was associated with better RFS. CONCLUSION Adjuvant treatment with imatinib for 3 years in patients with intermediate to high risk of recurrence was proven to prolong RFS, while being well-tolerated and not exhibiting a negative impact on patient compliance with therapy.
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- 2019
9. MP50-01 ARTIFICIAL INTELLIGENCE SUPPORTING CANCER PATIENTS ACROSS EUROPE- THE ASCAPE PROJECT
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Lazaros Tzelves, Ioannis Manolitsis, Mirjana Ivanović, Antonios Valachis, Paris Kosmidis, Lucian Mihai Itu, Serge Autexier, Konstantinos Perakis, Andreas Skolarikos, Athanasios Anastasiou, Ioannis M. Varkarakis, Johannes Rust, and Thanos Kosmidis
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Gerontology ,business.industry ,Urology ,030232 urology & nephrology ,Cancer ,urologic and male genital diseases ,medicine.disease ,Annual incidence ,3. Good health ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Quality of life (healthcare) ,030220 oncology & carcinogenesis ,medicine ,business - Abstract
INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) is one of the most common neoplasms in Europe, with annual incidence of 336.000. PCa patients frequently encounter health-related quality of life (Q...
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- 2021
10. Genotyping KRAS and EGFR Mutations in Greek Patients With Non-small-cell Lung Cancer: Incidence, Significance and Implications for Treatment
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Kotoula, Ioannis Efstratiou, E Res, Sofia Lampaki, Paris Kosmidis, Despoina Televantou, Kyriaki Papadopoulou, G. Fountzilas, Emily Daskalaki, X. Mavropoulou, Grigorios Rallis, H. Linardou, Karavasilis, Samantas E, Anna Kalogera-Fountzila, Dimitrios Pectasides, Kostas N. Syrigos, George Kouvatseas, Thomas Zaramboukas, and Mountzios G
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Genotyping Techniques ,medicine.disease_cause ,Biochemistry ,Disease-Free Survival ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Genotype ,Genetics ,medicine ,Humans ,Lung cancer ,neoplasms ,Molecular Biology ,Genotyping ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Histology ,Middle Aged ,medicine.disease ,digestive system diseases ,respiratory tract diseases ,ErbB Receptors ,Survival Rate ,030220 oncology & carcinogenesis ,Mutation ,Adenocarcinoma ,Female ,Non small cell ,KRAS ,business ,Research Article ,Follow-Up Studies - Abstract
Background/Aim: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC) and their prognostic role is unclear. We studied KRAS and EGFR genotyping in Greek NSCLC patients. Patients and Methods: KRAS and EGFR genotypes were centrally evaluated in 421 NSCLC patients (diagnosed September 1998 -June 2013) and associated with clinicopathological parameters. Outcome comparisons were performed in 288 patients receiving first line treatment. Results: Most patients were male (78.6%), >60 years old (63.9%), current smokers (51.1%), with adenocarcinoma histology (63.9%). EGFR and KRAS mutations were found in 10.7% and 16.6% of all histologies, respectively, and in 14.9% and 21.9% of adenocarcinomas. At 4.5 years median follow-up, KRAS status was an independent negative prognostic factor for overall survival (OS, p=0.016). KRAS mutations conferred 80% increased risk of death in patients receiving first-line treatment (p=0.002). Conclusion: The presence of KRAS mutations is an independent negative prognosticator among Greek NSCLC patients and an independent response predictor to first line treatment.
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- 2019
11. FP02.04 Immunotherapy in Lung Cancer: Analysis of Patients’ Awareness and Perceptions
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C. Lagogianni, T. Kosmidis, and Paris Kosmidis
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,Immunotherapy ,business ,Lung cancer ,medicine.disease - Published
- 2021
12. P54.01 Analysis of the Support Needs of Lung Cancer Patients
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C. Lagogianni, T. Kosmidis, and Paris Kosmidis
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Lung cancer ,medicine.disease - Published
- 2021
13. 1698P Analysis of patient-reported incidence of side-effects, and their improvement through online platforms
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Paris Kosmidis, C. Lagogianni, and T. Kosmidis
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medicine.medical_specialty ,Oncology ,business.industry ,Incidence (epidemiology) ,Emergency medicine ,Medicine ,Hematology ,business - Published
- 2021
14. 1490P Depression and anxiety in prostate cancer patients: Analysis of possible factors and correlations
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Paris Kosmidis, T. Kosmidis, and C. Lagogianni
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Oncology ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Internal medicine ,Medicine ,Anxiety ,Hematology ,medicine.symptom ,business ,medicine.disease ,Depression (differential diagnoses) - Published
- 2021
15. Impact of Bevacizumab
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Giannis, Mountzios, Xanthippi, Mavropoulou, Georgia-Angeliki, Koliou, Helena, Linardou, Epaminontas, Samantas, Paris, Kosmidis, George, Fountzilas, Aphrodite, Charitandi, and Anna, Kalogera-Fountzila
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Adult ,Male ,Docetaxel ,Middle Aged ,Disease-Free Survival ,Bevacizumab ,Erlotinib Hydrochloride ,Treatment Outcome ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Aged ,Neoplasm Staging - Abstract
The mechanism of action of bevacizumab and erlotinib is quite different in the treatment of advanced non-small cell lung cancer (NSCLC). This study sought to compare the two targeted therapies in terms of sequential tumor response metrics.Parameters of radiological tumor response evaluation were assessed at baseline and periodically in 58 patients receiving either bevacizumab plus platinum-based chemotherapy (N=25) or erlotinib (N=33).Bevacizumab-treated patients had lower longest diameter at best response compared to the erlotinib group (p=0.011). The longest diameter, tumor volume and density significantly decreased from baseline to best response for the entire cohort and bevacizumab-treated patients; no difference was found in the erlotinib group.Treatment with bevacizumab substantially improved tumor metrics between baseline and each cycle of treatment, as well as between baseline and best response, in patients with advanced NSCLC.
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- 2020
16. Outcomes from salvage chemotherapy or pembrolizumab beyond progression with or without local ablative therapies for advanced non-small cell lung cancers with PD-L1 ≥50% who progress on first-line immunotherapy: real-world data from a European cohort
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Marina Chiara Garassino, Alfredo Addeo, Giuseppe Luigi Banna, Helena Linardou, Fausto Roila, Giannis Mountzios, Diego Signorelli, Panagiota Economopoulou, Andrea Camerini, Alessio Gili, Ana Collazo-Lorduy, Juliana Rey Cobo, Giuseppe Lo Russo, Giulio Metro, Alessandro De Toma, Athina Christopoulou, Beatriz Jimenez, Domenico Galetta, Marco Banini, Panagiotis Baxevanos, Paris Kosmidis, and Antonio Calles
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,Non-small cell lung cancer (NSCLC) ,Pembrolizumab ,Local ablative therapy ,PD-L1 ≥50% ,Pembrolizumab beyond progression ,Salvage chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030212 general & internal medicine ,Chemotherapy ,Performance status ,business.industry ,medicine.disease ,Radiation therapy ,Regimen ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Original Article ,business ,Progressive disease - Abstract
Background: In this real-world multicenter study we addressed the activity of post-progression anticancer treatments after first-line pembrolizumab in advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥50%. Methods: Clinico-pathological data of PD-L1 ≥50% advanced NSCLCs who failed first-line pembrolizumab were collected in 14 Oncologic Centers from different European countries. Types of subsequent anticancer treatment and outcomes on salvage chemotherapy or pembrolizumab beyond progression with or without the addition of local ablative therapies were reported. Results: Out of 173 patients, 100 had progressed on pembrolizumab, of which 60 patients (60%) met eligibility criteria and were treated with either salvage chemotherapy (42/60, 70%) or pembrolizumab beyond progression (18/60, 30%). Overall, median age was 66 years, 63.3% were male, 60.0% had a performance status of 0–1, 88.3% were smokers and 61.7% had adenocarcinoma histology. In patients evaluable for response, objective response rate to salvage chemotherapy was 41.9%, with no significant difference according to the type of regimen (42.9% for platinum-based and 40.0% for single-agent chemotherapy). Median progression-free survival (PFS) to salvage chemotherapy was 4.5 months. Among patients treated with pembrolizumab beyond progression, 13 out of 18 patients (72.2%) had progressive disease in ≤2 organ sites, of whom 9 (69.2%) were managed with the addition of local ablative therapies consisting of radiation at progressive lesion(s). No significant difference was noted in terms of post-progression survival between the salvage chemotherapy and the pembrolizumab beyond progression groups of patients (6.9 versus 8.1 months, respectively, P=0.08). Conclusions: In PD-L1 ≥50% advanced NSCLCs who progress on first-line pembrolizumab, salvage chemotherapy is associated with a remarkable anticancer activity, while select patients may benefit from continuation of pembrolizumab beyond progression, with the possible addition of local ablative radiotherapy in oligoprogressive cases.
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- 2020
17. 118P The clinical utility of advanced lung inflammation index (ALI) for immunotherapy guidance in non-small cell lung cancer
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Giannis Mountzios, Johannes Krisam, Amanda Psyrri, I. Boukovinas, Fjf Herth, Paris Kosmidis, Kostas N. Syrigos, E. Razis, Helena Linardou, Thomas Muley, S. Angelaki, Martin Reck, K. Senghas, G. Pentheroudakis, Mike Thomas, Petros Christopoulos, Michael Meister, A. Stenzinger, Epaminontas Samantas, and Rami A. El-Shafie
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Inflammation ,Immunotherapy ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,medicine ,Non small cell ,medicine.symptom ,business ,Lung cancer - Published
- 2021
18. P75.04 Advanced Lung Cancer Inflammation Index (ALI), Neutrophil-to-Lymphocyte Ratio (NLR), and PD-(L)1 Inhibitor Efficacy in NSCLC
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M. Elshiaty, Michael Meister, C. Andreadis, Lena Gaissmaier, Ilias Athanasiadis, Farastuk Bozorgmehr, K. Samitas, A. Stenzinger, Helena Linardou, Giannis Mountzios, Georgios Pentheroudakis, Epaminontas Samantas, Sofia Baka, Harland S. Winter, Martin Reck, Helge Bischoff, Sophia Agelaki, K. Senghas, Georgios Oikonomopoulos, E. Zervas, J. Kuon, Mark Kriegsmann, L. Daniello, Paris Kosmidis, Anastasia Christopoulou, Amanda Psyrri, C.P. Heussel, Kostas N. Syrigos, E.-I. Perdikouri, Fjf Herth, E. Razis, Michael Thomas, R. El Shafie, Thomas Muley, Petros Christopoulos, Christos Emmanouilidis, Z. Saridaki, E. Lianos, I. Boukovinas, Johannes Krisam, Elena Fountzilas, and Katharina Kriegsmann
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,Inflammation ,medicine.symptom ,Neutrophil to lymphocyte ratio ,Lung cancer ,medicine.disease ,business ,Gastroenterology - Published
- 2021
19. Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer
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Sophia Agelaki, Johannes Krisam, K. Samitas, Christos Emmanouilides, Georgios Oikonomopoulos, C. Andreadis, C.P. Heussel, Ilias Athanasiadis, Katharina Kriegsmann, Farastuk Bozorgmehr, Epaminontas Samantas, Sofia Baka, Kostas N. Syrigos, J. Kuon, Giannis Mountzios, Georgios Pentheroudakis, L. Daniello, Helge Bischoff, Fjf Herth, A. Stenzinger, Petros Christopoulos, Amanda Psyrri, A. Christopoulou, Z. Saridaki, Elena Fountzilas, I. Boukovinas, Paris Kosmidis, M. Elshiaty, Michael Thomas, Harland S. Winter, Michael Meister, E. Lianos, E.-I. Perdikouri, E. Razis, L. Gaissmaier, Helena Linardou, Martin Reck, K. Senghas, E. Zervas, Mark Kriegsmann, R. El Shafie, and Thomas Muley
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PD-L1 ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,advanced lung cancer inflammation index ,neutrophil-to-lymphocyte ratio ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Neutrophil to lymphocyte ratio ,Lung cancer ,Immune Checkpoint Inhibitors ,Original Research ,Retrospective Studies ,Inflammation ,Chemotherapy ,biology ,business.industry ,Proportional hazards model ,Hazard ratio ,Retrospective cohort study ,Immunotherapy ,medicine.disease ,respiratory tract diseases ,non-small-cell lung cancer ,biology.protein ,immunotherapy ,business - Abstract
Background The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). Patients and methods This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. Results High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. Conclusions The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy., Highlights • ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy. • Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN). • For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.
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- 2021
20. P09.06 Patient Behaviors and Attitudes Towards Lung Cancer Medication Adherence
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Paris Kosmidis, T. Kosmidis, and C. Lagogianni
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,Medication adherence ,Lung cancer ,medicine.disease ,business - Published
- 2021
21. 1510MO European cancer patients’ perspectives on Immunotherapy
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T. Kosmidis, C. Lagogianni, and Paris Kosmidis
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Internal medicine ,Medicine ,Cancer ,Hematology ,Immunotherapy ,business ,medicine.disease - Published
- 2021
22. Efficacy analysis of a remote symptom management platform
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Christie Lagogianni, Paris Kosmidis, and Thanos Kosmidis
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Cancer Research ,medicine.medical_specialty ,Quality of life (healthcare) ,Oncology ,business.industry ,Multidisciplinary approach ,Symptom management ,Medicine ,Cancer ,business ,Intensive care medicine ,medicine.disease - Abstract
1566 Background: Quality of life of cancer patients is a critical part of cancer care. Symptom management is evolving as a multidisciplinary approach, and is increasingly delivered through a combination of physical and remote interactions. CareAcross is an online platform offering personalized, guidelines-based support to cancer patients, that complements physicians’ support and enables remote monitoring. This analysis investigated the improvement in the quality of life of cancer patients delivered through such remote support. Methods: Patients engage with an online interactive platform to receive personalized support based on a variety of parameters, through algorithms incorporating their exact diagnoses, treatments and comorbidities, and more. For symptom management, patients report the presence of specific side-effects via brief questionnaires; for each side-effect reported, they receive tailored support (text and multimedia) to help overcome it. These online questionnaires are repeated periodically to capture the outcome of the supportive process, and provide additional support as necessary. A retrospective analysis evaluated the efficacy of the personalized support: each patient’s reported side-effects were compared before versus after receiving the support, hence calculating the reduced incidence. Results: 2203 patients from 8 countries, with breast, lung, prostate or colorectal cancer (1563, 404, 159 and 77, respectively) reported side-effects, received support, and updated their reports at least once. The median follow-up period was 4.9 months. The patient-reported outcomes on their quality of life revealed substantial improvement, regardless of cancer type (lowest recorded improvement = 25.7%). Commonly reported side-effects included sleep problems, dry mouth, constipation, changes in food taste, and more (see Table). Side-effects reported in specific cancer types also showed substantial improvement, including hot flushes (breast; 32.0% improvement), dyspnea (lung; 38.1%), bowel dysfunction (prostate; 80%) and others. The efficacy of the support to breast, prostate or colorectal cancer patients was similar; support to lung cancer patients exhibited the lowest efficacy (p < 0.05). Fatigue was the most common side-effect. It was also the most resistant to improvement compared to all others (p < 0.05). Conclusions: Digital remote support of cancer patients is a realistic option to improve quality of life. Randomized controlled trials can help quantify its impact on health economics, hospital admissions, resource utilization, and other aspects.[Table: see text]
- Published
- 2021
23. Abstract OT-39-01: Artificial intelligence supporting cancer patients across Europe - the ASCAPE project for breast cancer patients
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Antonios Valachis, Paris Kosmidis, Imma Grau, Konstantinos Perakis, Montserrat Muñoz, Thanos Kosmidis, Miloš Savić, Dusan Jakotevic, Lucian Mihai Itu, Johannes Rust, and Serge Autexier
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Cancer Research ,Longitudinal study ,Health economics ,business.industry ,Psychological intervention ,Cancer ,medicine.disease ,3. Good health ,Breast cancer ,Oncology ,Quality of life ,Health care ,medicine ,Artificial intelligence ,business ,Prospective cohort study - Abstract
Background Many breast cancer patients experience adverse effects of cancer or treatment, which can considerably decrease quality of life (QoL). The current strategy of supporting breast cancer patients does not meet their needs due to the limited personalized-based approach in rehabilitation plan and the lack of healthcare, financial and other resources. ASCAPE (Artificial intelligence Supporting CAncer Patients across Europe) is a collaborative research project involving 15 partners from 7 countries, including academic medical centers, small and medium-sized enterprises, research centers and universities, aiming to leverage the recent advances in Big Data and AI (Artificial Intelligence) to support cancer patients’ QoL and health status. Specifically, ASCAPE aims to provide personalized- and AI-based predictions for QoL issues in breast cancer patients as well as suggest potential interventions to their physicians. Trial design During the first part of the project, large-scale retrospective datasets with breast cancer patients will be analyzed to develop and train AI-based models for specific QoL issues. During the second part of the project, a multicenter prospective longitudinal study is planned. Eligible patients will be followed for one year with validated questionnaires regarding different QoL issues, and wearables that will collect active monitoring data on physical activity, sleep pattern, and heart rate. The collected data will be used to further train and optimize the AI-based models and personalized-based intervention suggestions.Based on the retrospective and prospective data, an ASCAPE-integrated prototype will be developed, enabling personalized- and AI-based predictions and intervention suggestions. This approach will be evaluated at the end of the prospective study regarding patients´ and physicians´ experience as well as health economics. Eligibility criteria Breast cancer patients planned for curative treatment with surgery with or without oncological therapy or breast cancer patients at least 1 year post-treatment (except endocrine therapy) will be eligible for the prospective study. Specific aims 1.To develop and optimize AI-based predictions for QoL issues in breast cancer patients as well as potential intervention suggestions.2.To evaluate the AI-based follow-up approach for breast cancer survivors in terms of patients´ experience, physicians´ experience, and health economics. Statistical methods For discrete QoL outcome variables, ASCAPE will examine the efficiency of classification-based machine learning models trained using decision tree learning algorithms, nearest-neighbors based algorithms, probabilistic learning algorithms, support vector machines and (deep) neural networks. Regressive counterparts of aforementioned methods will be analyzed for numeric QoL outcome variables including also regression specific methods (e.g., ridge regression, lasso regression and elastic net regression). The accuracy of trained models will be estimated relying on standard machine learning validation procedures such as the K-fold cross-validation and leave-one-out cross-validation. The ASCAPE platform will utilize state-of-the-art explainability techniques to make the machine learning models’ predictions transparent and comprehensible for the patient and the physician.Present accrual and target accrual Four retrospective datasets will be used for the first part of the project including approximately 18,000 breast cancer patients. For the prospective study, it is planned to be included about 30 patients monthly during a period of 12 months. Contact information for people with a specific interest in the trial https://ascape-project.eu/artificial-intelligence-supporting-cancer-patients-across-europe Citation Format: Antonios Valachis, Serge Autexier, Imma Grau, Lucian Itu, Dusan Jakotevic, Thanos Kosmidis, Montserrat Muñoz, Konstantinos Perakis, Johannes Rust, Milos Savic, Paris Kosmidis. Artificial intelligence supporting cancer patients across Europe - the ASCAPE project for breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-39-01.
- Published
- 2021
24. Poor performance status and front-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC) patients with PD-L1>50%
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Diego Signorelli, Marina Chiara Garassino, Andrea Camerini, A. Christopoulou, Paris Kosmidis, Ana Collazo, Giuseppe Luigi Banna, Giannis Mountzios, Antonio Calles, Panagiotis Baxevanos, Beatriz Jimenez Munarriz, Fausto Roila, Domenico Galetta, Giulio Metro, Alessandro De Toma, Alfredo Addeo, Alex Friedlaender, Giuseppe Lo Russo, Panagiota Economopoulou, and Helena Linardou
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,non-small cell lung cancer (NSCLC) ,Front line ,Pembrolizumab ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,PD-L1 ,medicine ,biology.protein ,Poor performance status ,business ,Lung cancer ,030215 immunology - Abstract
e21651 Background: We retrospectively analysed real-world clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression ( > 50%) and treated with first-line pembrolizumab, following the Keynote 024 regimen. In the recent PePS2 trial and Checkmate 817, we see that some patients with PS2 could benefit from a durable response to checkpoint inhibitors. However, current data does not suggest an improvement in median OS compared to historical data on chemotherapy in this setting. Methods: Data was collected by 16 participating centers. The trial was approved by local ethics committees and patients included signed a general consent form. All patients with NSCLC with PD-L1 expression ≥50%, treated with first-line pembrolizumab were included, from the introduction of first-line pembrolizumab to the present. We collected medical data from patient files, pathology reports and laboratory reports for all patients. Patient characteristics, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and tumor characteristics were reported. Overall survival (OS) was calculated from the date of the first cycle of pembrolizumab to death and estimated through the Kaplan-Meier method. Results: 302 patients were identified, of which 247 with a PS of 0-1, 52 with a PS of 2. Patients (3) with PS3 were excluded. The median age was 69 with a range from 19 to 87 years. There were 193 males and 106 females, 90% were active or former smokers, 19% had brain lesions at diagnosis. Only 14% received brain radiotherapy. Median OS was 7.2 months among patients with PS2, while not reached for those with PS0-1 (HR 3.80, 95% confidence interval 2.49-5.78). Conclusions: Patients with a PS of 2 had significantly worse survival than those with PS0-1. The retrospective nature of our trial and lack of a control arm treated with chemotherapy do not allow us to postulate as to whether PS is predictive or prognostic. Our data suggests worse survival among NSCLC patients with PS2 treated with front-line pembrolizumab. A prospective randomized trial comparing immunotherapy to chemotherapy or chemo-immunotherapy in this population would be welcome.
- Published
- 2020
25. Breast cancer patients’ quality of life: Real-world data
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Thanos Kosmidis, Barbara Athanasakou, and Paris Kosmidis
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Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Hematology ,Real world evidence ,medicine.disease ,Chemotherapy regimen ,Quality of life (healthcare) ,Breast cancer ,Oncology ,Quality of life ,Trastuzumab ,Internal medicine ,Medicine ,Medical physics ,business ,Adverse effect ,Real world data ,Triple-negative breast cancer ,medicine.drug - Abstract
Background CareAcross is a digital platform dedicated to support, inform and engage with cancer patients. It also collects medical and other data, and generates real world evidence. Methods In an effort to collect and analyze information from breast cancer patients regarding side effects in relation to their treatments and supplements intake, we contacted 5373 patients in the UK, Germany, France, Spain and Italy. 547 had triple negative breast cancer (TNBC) and the remaining 4826 had other breast cancer subtypes (non-TNBC). All data was collected anonymously, with strong privacy and security controls. Results Different regimens were given as adjuvant or as systemic treatments. AC treatment was given to 10% of TNBC vs 5% of non-TNBC patients; FEC-T to 18% vs 11%, FEC to 9% vs 7%, taxanes to 39% vs 22% and platinum-based chemotherapy to 14% vs 2%, respectively. Among non-TNBC patients, 12% received Trastuzumab and 52% received hormonal treatment. Some of the patients were asked regarding side effects as well as vitamins and supplements intake. Among them, 136 TNBC patients reported an average of 3.0 side effects (95% CI 2.6-3.5), 22% more than those reported by 1015 non-TNBC patients (2.5 side effects; 95% CI 2.4-2.6); p = 0.03. Similarly, an average of 3.6 vitamins and supplements was reported by 111 TNBC patients (95% CI 2.9-4.3), 15% more compared to 854 non-TNBC patients (3.1 supplements; 95% CI 2.9-3.3); p = 0.22. An analysis of the patients reporting at least 1 side-effect showed 120 TNBC patients with an average of 3.5 side effects (95% CI 3.0-3.9), 17% more than 862 non-TNBC patients (3.0 side effects, 95% CI 2.8-3.1); p = 0.05. Regarding consumption of at least 1 vitamin/supplement, the average intake across 85 TNBC patients was 4.7 (9.5% CI 3.9-5.5), 23% more than 697 non-TNBC patients (3.8 vitamins/supplements, 95% CI 3.5-4.0); p = 0.04. Conclusions The real world evidence obtained through an international analysis shows that TNBC patients receive more toxic treatments due to the aggressive disease, as expected. TNBC patients experience significantly more side effects compared to non-TNBC patients. They also consume more vitamins and supplements; the difference across patients reporting at least one vitamin/supplement was larger and statistically significant. Legal entity responsible for the study Care Across Ltd. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
- Published
- 2019
26. Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real-world data from a European Cohort with focus on subgroups of interest
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Helena Linardou, Beatriz Jimenez, M.C. Garassino, Domenico Galetta, Fausto Roila, Alfredo Addeo, Giulio Metro, Marco Banini, Giannis Mountzios, A. De Toma, Panagiota Economopoulou, A. Christopoulou, J Rey Cobo, Diego Signorelli, Andrea Camerini, Panagiotis Baxevanos, G. Lo Russo, Paris Kosmidis, Antonio Calles, and Giuseppe Luigi Banna
- Subjects
medicine.medical_specialty ,business.industry ,Age at diagnosis ,Hematology ,Oncology ,Steroid use ,Family medicine ,Cohort ,Medicine ,Pd l1 expression ,In patient ,Risk of death ,business ,Real world data ,Medically inoperable - Abstract
Background Real-world data regarding clinical outcomes associated with first-line pembrolizumab (pembro) monotherapy among specific subgroups of NSCLC patients are lacking. Methods A comprehensive clinicopathological database of patients with NSCLC and PD-L1>50% treated with frontline pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created. Post-progression outcomes have been previously reported. Clinical outcomes in specific subgroups of interest are presented in the current report. Analysis was performed using the SAS 9.3 software. Multivariate analysis was performed with the Cox regression model. Results Among 173 eligible patients, median age at diagnosis was 68 years, 65% were male, 88% were current or former smokers, 25% had an ECOG PS > =2, histology was 67% adeno, 21% squamous, 20% had brain mets, 15% had liver mets at diagnosis and 28% received steroids at the beginning and/or during treatment. Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. Hazard Ratios for OS, with corresponding 95% CIs and p-values for specific subgroups were as follows: Elderly patients ( >70 years): HR = 0.85 (0.52-1.38), p = 0.51; Brain mets: HR = 1.17 (0.63-2.18), p = 0.63; Stage I-IIIC: HR = 0.56 (0.22-1.39), p = 0.21; PS > =2: HR = 1.73 (1.55-1.84), p Conclusions Real-world data in a large retrospective cohort of patients with NSCLC and PD-L1>50% indicate that 1) Pembro frontline is also active in inoperable stage I-IIIC patients, 2) Elderly patients (>70 years) derive similar survival benefit to younger ones, except from those with PS > =2, 3) Steroid use at the beginning and/or during treatment is associated with a three-fold increase in the risk of death. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure G. Mountzios: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca Greece; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Greece; Honoraria (self), Travel / Accommodation / Expenses: Pfizer Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD Hellas; Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Greece. G. Banna: Advisory / Consultancy: Janssen; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Ipsen. A. Christopoulou: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PFIZER; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: NOVARTIS. H. Linardou: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Boehringer ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. A. Calles: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS. A. Addeo: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: BMS. P.A. Kosmidis: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Leo. M.C. Garassino: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche ; Honoraria (self), Advisory / Consultancy: PFIZER; Honoraria (self): MEDSCAPE; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD Hellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): GSK. All other authors have declared no conflicts of interest.
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- 2019
27. Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group
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Georgia Karayannopoulou, Apostolos Laskarakis, Elke Veltrup, George Fountzilas, Ralph M. Wirtz, George Pentheroudakis, Christos Christodoulou, Panagiota Economopoulou, Amanda Psyrri, Konstantine T. Kalogeras, Gerasimos Aravantinos, Pavlos Papakostas, Anna Batistatou, Dimitrios Pectasides, Petroula Arapantoni-Dadioti, Georgios Lazaridis, Anna Goussia, George Kouvatseas, Eleni Timotheadou, Maria Sotiropoulou, Angelos Koutras, Helen Gogas, Flora Zagouri, and Paris Kosmidis
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Survival ,medicine.medical_treatment ,mRNA ,Breast Neoplasms ,General Biochemistry, Genetics and Molecular Biology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,stomatognathic system ,Internal medicine ,medicine ,Humans ,Osteopontin ,RNA, Messenger ,Proportional Hazards Models ,Medicine(all) ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Research ,Matricellular protein ,qRT-PCR ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Clinical trial ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Real-time polymerase chain reaction ,030220 oncology & carcinogenesis ,Multivariate Analysis ,biology.protein ,Hormonal therapy ,Immunohistochemistry ,Female ,business ,Adjuvant ,Prognostic value ,IHC - Abstract
Background The shift towards an earlier diagnosis of breast cancer (BC) highlights the need for biomarkers that would identify patients at risk for relapse and metastatic spread and indicate the potential value of additional treatment strategies. Osteopontin (OPN) is a matricellular protein that has been suggested to be a potential biomarker in BC. In the present study, we used archived BC patient samples to assess the clinical utility of OPN. Methods Formalin-fixed paraffin-embedded tumor tissue samples from 975 patients were collected from two large phase III randomized adjuvant chemotherapy trials (HE10/97 and HE10/00) that included patients with high risk BC. All tissue samples were assessed for ER, PgR, Ki67 and HER2 protein expression. OPN protein and mRNA expression was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, respectively. Results OPN mRNA expression data were available for 814 patients, whereas OPN protein expression data were available for 546 patients. The majority of patients were ER/PgR-positive (78.3%), HER2-negative (76.5%) and Ki67-positive (55.2%) and had received adjuvant radiation therapy (76.8%) and hormonal therapy (81.1%). OPN mRNA expression was significantly associated with age (60.9% in high OPN tumors vs. 54.1% in low OPN tumors, p = 0.047), ER/PgR-negative status (25.7 vs. 17.2%, p = 0.004) and BC subtypes (p = 0.021). In addition, high OPN mRNA expression was significantly associated with reduced DFS (HR 1.26, 95% CI 1.00–1.59, Wald’s p = 0.050) and OS (HR 1.37, 95% CI 1.05–1.78, p = 0.019), while it retained its prognostic significance for both DFS (HR 1.39, 95% CI 1.10–1.77, p = 0.007) and OS (HR 1.54, 95% CI 1.61–2.05, p = 0.003) in the multivariate analysis. Conclusions We showed that high OPN mRNA expression is associated with decreased DFS and OS in a large cohort of BC patients treated with adjuvant chemotherapy in a clinical trial setting. Our results suggest that OPN may serve as a prognostic factor and a potential target for therapy. Trial registration Australian New Zealand Clinical Trials Registry; HE10/97 ACTRN12611000506998; HE10/00 ACTRN12609001036202
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- 2016
28. P1.16-09 Post-Progression Outcomes After Pembrolizumab in Patients with NSCLC and High PD-L1 Expression: Real-World Data from a European Cohort
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Beatriz Jimenez, Marina Chiara Garassino, Diego Signorelli, Domenico Galetta, Andrea Camerini, Giuseppe Luigi Banna, Giannis Mountzios, A. Calles Blanco, J. Rey-Cobo, Panagiotis Baxevanos, Marco Banini, Paris Kosmidis, G. Lo Russo, A. Christopoulou, Ana Collazo-Lorduy, Fausto Roila, A. De Toma, Alfredo Addeo, Giulio Metro, Panagiota Economopoulou, and Helena Linardou
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Cohort ,medicine ,In patient ,Pd l1 expression ,Pembrolizumab ,business ,Real world data - Published
- 2019
29. Treatment of bone metastases before the onset of pain
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Peyman Hadji, Luis Costa, Allan Lipton, Yin Miao Chen, and Paris Kosmidis
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Male ,medicine.medical_specialty ,Lung Neoplasms ,Pain ,Bone Neoplasms ,Breast Neoplasms ,Zoledronic Acid ,Asymptomatic ,Surgical oncology ,Internal medicine ,Humans ,Medicine ,Bone pain ,Aged ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Diphosphonates ,business.industry ,Imidazoles ,Structural integrity ,Hematology ,General Medicine ,Pain onset ,Middle Aged ,Surgery ,Increased risk ,Zoledronic acid ,Oncology ,Female ,Bisphosphonate therapy ,medicine.symptom ,business ,medicine.drug - Abstract
Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain.Exploratory analyses were performed in patients with bone metastases from breast cancer or lung cancer/other solid tumors enrolled in two randomized trials comparing monthly zoledronic acid versus pamidronate (breast cancer) or placebo (lung cancer/other solid tumors). Analyses included proportion of patients with one or more skeletal-related events, time to first skeletal-related event, and skeletal morbidity rate in patients with and without baseline pain.Approximately 80 % of patients reported baseline pain. Similar to overall trial results, zoledronic acid reduced the skeletal morbidity rate in all groups. Although some subsets lacked statistical power, benefits were generally greater in patients without baseline pain. For example, in breast cancer, zoledronic acid increased the 25th quartile of time to first skeletal-related event versus pamidronate by 522 days in patients with no baseline pain (median not reached for either group), but by only 10 days in patients with baseline pain. Similar trends were observed in lung cancer.Benefits from zoledronic acid appeared to be greater if introduced before bone pain onset. Early diagnosis and treatment of bone metastases may delay onset of skeletal-related events.
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- 2012
30. Third CECOG consensus on the systemic treatment of non-small-cell lung cancer
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Nick Thatcher, Jacek Jassem, Ch. Manegold, J.L. Pujol, Maciej Krzakowski, M. Filipits, Rolf A. Stahel, Christoph C. Zielinski, S. Zöchbauer-Müller, Fred R. Hirsch, Paris Kosmidis, J.R. Fischer, Vassilis Georgoulias, Jeffrey Crawford, R. Pirker, C. Minichsdorfer, Tudor-Eliade Ciuleanu, C. Gridelli, Johan Vansteenkiste, Thomas Brodowicz, University of Zurich, and Zielinski, C C
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Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,2720 Hematology ,MEDLINE ,610 Medicine & health ,Medical Oncology ,Targeted therapy ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Humans ,Medicine ,Lung cancer ,Societies, Medical ,Neoadjuvant therapy ,Chemotherapy ,business.industry ,Hematology ,Evidence-based medicine ,medicine.disease ,Chemotherapy regimen ,Metastatic breast cancer ,Neoadjuvant Therapy ,Surgery ,Review Literature as Topic ,10032 Clinic for Oncology and Hematology ,Practice Guidelines as Topic ,2730 Oncology ,business - Abstract
The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options.
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- 2012
31. P3.01-61 EGFR and KRAS Mutational Status and Significance in Greek Patients with Advanced Non Small Cell Lung Cancer
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E Res, Vasilios Karavasilis, Vasiliki Kotoula, Giannis Mountzios, Thomas Zaramboukas, Ioannis Efstratiou, Emily Daskalaki, D. Televantou, Paris Kosmidis, Kostas N. Syrigos, Dimitrios G. Pectasides, X. Mavropoulou, Kyriaki Papadopoulou, George Kouvatseas, Helena Linardou, A. Kalogera-Fountzila, Grigorios Rallis, George Fountzilas, Epaminontas Samantas, and Sofia Lambaki
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Pulmonary and Respiratory Medicine ,Oncology ,business.industry ,Cancer research ,Mutational status ,Medicine ,KRAS ,Non small cell ,business ,medicine.disease_cause ,Lung cancer ,medicine.disease - Published
- 2018
32. Correlation of MYC Gene and Protein Status With Breast Cancer Subtypes and Outcome of Patients Treated With Anthracycline-Based Adjuvant Chemotherapy. Pooled Analysis of 2 Hellenic Cooperative Group Phase III Trials
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Kalliopi Petraki, Anna Goussia, Gerasimos Aravantinos, Flora Zagouri, Eleftheria Tsolaki, George Pentheroudakis, Mattheos Bobos, Triantafyllia Koletsa, Paris Kosmidis, Anna Batistatou, Maria Sotiropoulou, Helen Gogas, Evangelia Razis, Vassiliki Kotoula, Dimitrios Pectasides, George Kouvatseas, George Fountzilas, Stavroula Pervana, Christos Papadimitriou, Eleni Timotheadou, and Angelos Koutras
- Subjects
Adult ,0301 basic medicine ,Cancer Research ,Anthracycline ,medicine.medical_treatment ,Breast Neoplasms ,Disease-Free Survival ,Proto-Oncogene Proteins c-myc ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,MYC Gene Amplification ,Chromosomal Instability ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Anthracyclines ,Breast ,Aged ,Cell Nucleus ,Chemotherapy ,Polysomy ,Antibiotics, Antineoplastic ,medicine.diagnostic_test ,business.industry ,Gene Amplification ,Middle Aged ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Paclitaxel ,chemistry ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Cancer research ,Immunohistochemistry ,Female ,business ,Fluorescence in situ hybridization - Abstract
Background The prognostic/predictive value of aberrant MYC gene copies and protein expression is not clear in breast cancer. Patients and Methods Early breast cancer patients were treated with anthracycline-containing chemotherapy within 2 randomized adjuvant trials. MYC gene and centromere-8 status, as well as Myc protein expression were investigated on 1060 paraffin tumors with fluorescence in situ hybridization and immunohistochemistry, respectively. Results MYC amplification was present in 45% and polysomy-8 in 23% of the tumors. Cytoplasmic staining was observed in 60% and nuclear staining in 26% of the tumors, strongly correlating with each other but not with MYC gene status. MYC gene amplification in the absence of polysomy-8 was associated with adverse disease-free survival (DFS) and overall survival (OS), and remained as an independent unfavorable prognostic factor in multivariate analysis (Wald P = .022 for DFS; P = .032 for OS), whereas patients with MYC amplification and polysomy-8, with polysomy-8 only, and with normal MYC without polysomy-8 performed significantly better compared with those with MYC gene amplification only. Nuclear Myc protein expression benefitted patients treated with paclitaxel (interaction P = .052 for DFS; P = .049 for OS). This interaction remained independently significant in multivariate analysis for OS (overall P = .028). Conclusion The effect of MYC gene status on breast cancer patient outcome seems to depend on the underlying chromosomal instability and appears unfavorable for tumors with MYC amplification without polysomy. Nuclear Myc protein expression seems predictive for benefit from adjuvant paclitaxel. These data might aid in the interpretation of relevant findings from large clinical trials.
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- 2018
33. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC
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Paris Kosmidis, Dimitrios Bafaloukos, Samuel S. Murray, Issa J Dahabreh, and Helena Linardou
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Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Colorectal cancer ,medicine.drug_class ,Somatic cell ,business.industry ,medicine.disease ,Monoclonal antibody ,medicine.disease_cause ,respiratory tract diseases ,ErbB Receptors ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Mutation ,medicine ,Carcinoma ,Humans ,Adenocarcinoma ,KRAS ,Lung cancer ,business ,Protein Kinase Inhibitors ,Tyrosine kinase - Abstract
Early clinical studies of tyrosine kinase inhibitors (TKIs) that target the EGFR in patients with advanced non-small-cell lung cancer (NSCLC) showed that some patients experienced rapid, durable, complete or partial responses. These data were the basis for attempts to identify specific subgroups of patients who would further benefit from these agents. The discovery of somatic mutations in EGFR that correlated with sensitivity to TKIs identified a plausible explanation for these observations. Clinical and pathological factors such as female sex, never having smoked, Asian origin and adenocarcinoma histology correlate with the presence of EGFR mutations and objective responses to TKIs in patients with NSCLC. Recent studies in metastatic colorectal cancer highlighted that somatic mutations in KRAS represent a negative predictor of response to anti-EGFR monoclonal antibodies; KRAS mutations also represent an important mechanism of resistance to TKIs in NSCLC. Many large clinical studies are currently investigating the predictive and prognostic value of EGFR mutational status and other candidate biomarkers. We summarize the literature and present an overview of the field of anti-EGFR therapy in NSCLC, focusing on the influence of somatic EGFR mutations on selection of patients for TKI therapy and the influence of EGFR pathway regulation.
- Published
- 2009
34. Carboplatin and Paclitaxel versus Cisplatin, Paclitaxel and Doxorubicin for first-line chemotherapy of Advanced Ovarian Cancer: A Hellenic Cooperative Oncology Group (HeCOG) study
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Dimitrios Bafaloukos, A. Onyenadum, Dimosthenis Skarlos, George P. Stathopoulos, Eleni Timotheadou, Paris Kosmidis, Alexandros Papanikolaou, Evangelos Briasoulis, Christos Papadimitriou, Haralabos P. Kalofonos, Irene Grimani, Aristotelis Bamias, Pavlos Papakostas, Epaminondas Samantas, Spyridon Rizos, Gerasimos Aravantinos, Dimitrios Pectasides, George Fountzilas, Meletios A. Dimopoulos, and Theofanis Economopoulos
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Oncology ,Cancer Research ,initial treatment ,medicine.medical_treatment ,cisplatin ,carcinoma ,chemotherapy ,stage-iii ,Carboplatin ,chemistry.chemical_compound ,Antineoplastic Combined Chemotherapy Protocols ,intergroup trial ,Aged, 80 and over ,Ovarian Neoplasms ,Middle Aged ,Treatment Outcome ,Paclitaxel ,carboplatin ,Female ,metaanalysis ,medicine.drug ,safety ,Adult ,medicine.medical_specialty ,Anthracycline ,anthracycline ,doxorubicin ,Internal medicine ,medicine ,Humans ,Doxorubicin ,Aged ,Neoplasm Staging ,Cisplatin ,Chemotherapy ,Performance status ,business.industry ,Regimen ,advanced ,chemistry ,Patient Compliance ,cyclophosphamide ,Epidemiologic Methods ,business ,phase-ii - Abstract
Introduction: The combination of Carboplatin and Paclitaxel is considered the standard of care as initial chemotherapy for Advanced Ovarian Cancer (AOC). We compared this regimen with the combination of Cisplatin, Paclitaxel and Doxorubicin. Patients and methods: Patients with AOC were randomised to either six courses of Paclitaxel 175 mg/m(2) plus Carboplatin 7AUC or Paclitaxel at the same dose plus Cisplatin 75 mg/m(2) plus Doxorubicin 40 mg/m(2). Results: Analysis was performed on 451 patients. The treatment groups were well balanced with regard to patient and disease characteristics. Performance status (PS) was better in the anthracycline arm. In terms of severe toxicity, the only significant difference between the two groups was the development of febrile neutropaenia in the anthracycline arm. Overall response rate was similar in both groups. With a median follow-up of 57.5 months, a marginal significance towards improved Progression-Free Survival (PFS) was noted in favour of the anthracycline arm, whilst there was no difference in overall survival. In multivariate analysis the hazard of disease progression at any time was significantly decreased by 25.5% for patients of the anthracycline arm. Conclusion: The combination of Cisplatin, Paclitaxel and Doxorubicin demonstrates a marginal PFS improvement, but no additional survival benefit when compared with the standard Carboplatin/Paclitaxel regimen. (c) 2008 Elsevier Ltd. All rights reserved. European Journal of Cancer
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- 2008
35. Somatic Mutations of the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor and Tyrosine Kinase Inhibitor Response to TKIs in Non-small Cell Lung Cancer: An Analytical Database
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Dimitrios Bafaloukos, Paris Kosmidis, Menelaos Manoloukos, Helena Linardou, Samuel S. Murray, and Issa J Dahabreh
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Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Databases, Factual ,medicine.drug_class ,Somatic cell ,Adenocarcinoma ,computer.software_genre ,Tyrosine-kinase inhibitor ,Erlotinib Hydrochloride ,Gefitinib ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Epidermal growth factor receptor ,Lung cancer ,Protein Kinase Inhibitors ,Database ,biology ,business.industry ,Smoking ,medicine.disease ,Prognosis ,respiratory tract diseases ,ErbB Receptors ,Treatment Outcome ,Erlotinib ,Oncology ,Mutation ,Cancer research ,biology.protein ,Quinazolines ,business ,computer ,Tyrosine kinase ,medicine.drug - Abstract
Background After the discovery of somatic mutations in the tyrosine kinase domain (exons 18–24) of the epidermal growth factor receptor (EGFR) correlating with responses of non-small cell lung cancer (NSCLC) to the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, there has been increasing interest in utilizing this molecular marker for treatment selection. We aimed to analytically catalogue the mutational spectrum of somatic mutations in EGFR and format a database allowing correlation of specific mutations with clinico-pathologic factors and response to TKIs. Methods A computerized search of MEDLINE (January 1, 2004 to June 30, 2007) was performed to identify articles reporting on NSCLC patients harboring somatic mutations in EGFR. Demographic, clinico-pathologic, mutational, and response data were extracted and tabulated. Results A total of 202 eligible articles were identified. We report data on 12,244 patients with 3381 somatic EGFR mutations. The majority of mutations have been reported on only one occasion (158 of 254, 62.2%), and only nine mutations occur at a rate of ≥1%. L858R and delE746-A750 account for 32.84% and 24.28% of all mutations, respectively; with 50% of mutations being exon 19 deletions or "deletional-insertions." There is a clear association between the presence of mutations and response to TKI. Conclusions We have generated a free access, nonprofit online analytical database of somatic EGFR mutations in NSCLC. Cumulative information will be made available through a routine update of both database tables and associated graphical representations. Direct updates and submissions through the online site (www.somaticmutations-EGFR.org) are encouraged, as are comments and suggestions.
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- 2008
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36. Paclitaxel, epirubicin, and carboplatin in advanced or recurrent endometrial carcinoma: A Hellenic Co-operative Oncology Group (HeCOG) study
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Paris Kosmidis, Christos Papadimitriou, Gerassimos Aravantinos, Dimitrios Bafaloukos, Haralambos P. Kalofonos, George Bozas, George Fountzilas, and Meletios A. Dimopoulos
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Adult ,Oncology ,medicine.medical_specialty ,Paclitaxel ,medicine.medical_treatment ,Adenocarcinoma ,Neutropenia ,Endometrium ,Carboplatin ,chemistry.chemical_compound ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Carcinoma ,Humans ,Aged ,Epirubicin ,Neoplasm Staging ,Chemotherapy ,Greece ,business.industry ,Patient Selection ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Carcinoma, Papillary ,Endometrial Neoplasms ,medicine.anatomical_structure ,chemistry ,Injections, Intravenous ,Toxicity ,Female ,business ,Adenocarcinoma, Clear Cell ,medicine.drug - Abstract
Objective Taxanes, anthracyclines, and platinum compounds represent the chemotherapeutic agents with the greatest activity in metastatic endometrial carcinoma. We administered the combination of paclitaxel, epirubicin and carboplatin to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity. Methods Sixty-three consecutive patients were treated on an outpatient basis with epirubicin 50 mg/m 2 , followed by paclitaxel 150 mg/m 2 , administered intravenously over a 3-h period. Subsequently, the patients received carboplatin at AUC of 5. The chemotherapy was repeated every 3 weeks with granulocyte colony-stimulating factor (G-CSF) support for a maximum of six courses. Results Response was assessed among 56 eligible patients. Thirty-six (63.2%) patients achieved objective clinical response (95% CI, 50.6–75.7%) including 14 (24.6%) complete and 22 (38.6%) partial responses. The median duration of response was 7.9 months, and the median times to progression and survival for all patients were 7.8 and 13.8 months, respectively. Grade 3 or 4 neutropenia occurred in 9 (15.5%) patients but only 3 episodes of neutropenic fever were encountered. Grade 2 or 3 neurotoxicity was observed in 19% of patients. Two patients died of sudden cardiac death 10 and 14 days after the administration of the first chemotherapy cycle, respectively, but these deaths were not clearly treatment related. Conclusions The combination of paclitaxel, epirubicin and carboplatin with G-CSF support appears active in patients with metastatic or recurrent carcinoma of the endometrium.
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- 2008
37. Gemcitabine Combined with Gefitinib in Patients with Inoperable or Metastatic Pancreatic Cancer: A Phase II Study of the Hellenic Cooperative Oncology Group with Biomarker Evaluation
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Helena Linardou, Christos Christodoulou, Mattheos Bobos, Samuel S. Murray, Nikolaos Xiros, George Fountzilas, Theofanis Economopoulos, Paris Kosmidis, Dimitrios Bafaloukos, Georgia Karayannopoulou, Konstantine T. Kalogeras, Angelos Koutras, Anna Kalogera-Fountzila, and Epaminondas Samantas
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Phases of clinical research ,Adenocarcinoma ,Deoxycytidine ,Disease-Free Survival ,Proto-Oncogene Proteins p21(ras) ,Gefitinib ,Proto-Oncogene Proteins ,Pancreatic cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Bone Marrow Diseases ,Survival rate ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,PTEN Phosphohydrolase ,Genes, erbB-1 ,General Medicine ,Genes, erbB-2 ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Gemcitabine ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Genes, ras ,Toxicity ,Quinazolines ,ras Proteins ,Biomarker (medicine) ,Female ,business ,medicine.drug - Abstract
The combination of gemcitabine and gefitinib was evaluated in advanced pancreatic cancer. Totally, 53 patients were treated with a 7 week cycle of gemcitabine (1,000 mg/m(2) given weekly) followed by six 4 week cycles of gemcitabine given on days 1, 8 and 15. Gefitinib 250 mg was administered daily. Responses were seen in 6, and stabilization of the disease in 12 patients. The main toxicity was myelotoxicity (92%). The 6-month progression-free survival (PFS) was 30%. Median PFS was 4.1 months and median survival 7.3 months with a 1 year survival rate of 27%. The above combination demonstrated promising activity in advanced pancreatic cancer.
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- 2008
38. Gemcitabine versus Gemcitabine–Carboplatin for Patients with Advanced Non-small Cell Lung Cancer and a Performance Status of 2: A Prospective Randomized Phase II Study of the Hellenic Cooperative Oncology Group
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C. Bacoyiannis, C. Nicolaides, Konstantinos N. Syrigos, Dimitrios G. Pectasides, Gerasimos Aravantinos, H. P. Kalofonos, Paris Kosmidis, Dimitrios Bafaloukos, Meletios-Athanasios Dimopoulos, I. Boukovinas, and George Fountzilas
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Phases of clinical research ,Antineoplastic Agents ,Clinical benefit ,Neutropenia ,Deoxycytidine ,Severity of Illness Index ,Gastroenterology ,Carboplatin ,chemistry.chemical_compound ,Non-small cell lung cancer ,Performance status of 2 ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Chemotherapy ,Humans ,Lung cancer ,Aged ,Aged, 80 and over ,Performance status ,business.industry ,Area under the curve ,Middle Aged ,medicine.disease ,Gemcitabine ,Surgery ,Treatment Outcome ,Oncology ,chemistry ,Female ,business ,medicine.drug - Abstract
Background:The purpose of this study was to evaluate gemcitabine–carboplatin (GCb) versus single-agent gemcitabine (G) in patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) of 2. The primary endpoint was clinical benefit.Patients and Methods:Patients were randomly assigned to either 1250 mg/m2 of G (arm A) or 1250 mg/m2 of G plus carboplatin area under the curve of 3 (arm B). Both treatments were given on days 1 and 14 and were repeated every 28 days for up to four cycles.Results:Among the 90 eligible patients (47 in arm A and 43 in arm B), in arm A, two (4%) had partial responses (95% CI, 0.52%–14.5%) and 10 (21%) had stable disease (95% CI, 10.7%–35.7%). In arm B, six (14%) had partial responses (95% CI, 5.3%–27.9%) and nine (21%) had stable disease (95% CI, 10%–36%) (p = 0.14). No significant difference was found in terms of clinical benefit between the two treatment groups after two cycles of treatment or at the end of chemotherapy. Furthermore, no association was found between clinical benefit and response to treatment (p > 0.05). Median survival was 4.8 months (95% CI, 2.45–7.25) for arm A and 6.7 months (95% CI, 2.47–10.8) for arm B (p = 0.49). Neutropenia (p = 0.007) and thrombocytopenia (p < 0.001) were more common in group B. Nevertheless, no significant differences were found in terms of severe toxicities (p > 0.05 in all cases).Conclusion:No significant difference was found in terms of clinical benefit in patients with NSCLC and PS 2 who received single-agent G or GCb. Nevertheless, GCb caused more toxicity, particularly neutropenia and thrombocytopenia.
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- 2007
39. Impact of tumor angiogenic profile on the outcome of patients with metastatic breast carcinoma treated with weekly docetaxel. A Hellenic Cooperative Oncology Group (HeCOG) study
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Helen P, Kourea, Vassiliki, Kotoula, Angelos, Koutras, Zoi, Alexopoulou, Irene, Papaspirou, Dimosthenis V, Skarlos, Ioannis, Efstratiou, Mattheos, Bobos, Flora, Zagouri, Pavlos, Papakostas, Dimitrios, Pectasides, Sofia, Chrisafi, Ioannis, Varthalitis, Gerasimos, Aravantinos, Paris, Kosmidis, Dimitrios, Bafaloukos, Chrisoula D, Scopa, and George, Fountzilas
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Adult ,Aged, 80 and over ,Neovascularization, Pathologic ,Antineoplastic Agents ,Breast Neoplasms ,Docetaxel ,Kaplan-Meier Estimate ,Middle Aged ,Immunohistochemistry ,Polymerase Chain Reaction ,Disease-Free Survival ,Treatment Outcome ,Biomarkers, Tumor ,Humans ,Female ,Taxoids ,Prospective Studies ,Aged ,Oligonucleotide Array Sequence Analysis ,Retrospective Studies - Abstract
Metronomic taxane administration has putative antiangiogenic properties. Herein, we examined the baseline tumor angiogenic profile of patients with metastatic breast carcinoma (MBC) in a prospective-retrospective translational research study. The interplay between the angiogenic factors expressed in the tumors and their prognostic value in MBC were investigated.Tumor tissues from patients with MBC treated with weekly docetaxel (n=159) were examined by immunohistochemistry for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, VEGFR-3 and osteopontin (OPN) and by mRNA analysis for expression of VEGF-A, VEGFxxxa, VEGFxxxb, VEGF-C, thrombospondin-1 (THBS-1), hypoxia-inducible factor-1α (HIF-1α) and von Hippel-Lindau (VHL) genes. Associations between these parameters and outcome were statistically analyzed.Statistically significant correlations were identified between almost all biomarkers examined in continuous form, particularly at the mRNA level: VEGF-A with VEGFxxxa (rho=0.70); VEGF-C with VEGFxxxa, VEGFxxxb and VHL (rho=0.51, 0.60 and 0.44 respectively); HIF-1α with VEGF-C and THBS1 (rho= 0.48 and 0.45). High VEGF-A mRNA was associated with worse survival (p=0.0279) and marginally with progression free survival (PFS). Intratumoral co-expression of VEGFR-1 and VEGFR-2 proteins was associated with more favorable survival (p=0.0337). In multivariate analysis, only high VEGF-A mRNA levels retained their prognostic role for worse PFS and survival (PFS: HR=2.34, 95% CI=1.25-4.40, p=0.0080; survival: HR=3.15, 95% CI=1.48-6.72, p=0.0029).In MBC, this study confirms the adverse prognostic effect of high intratumoral VEGF-A mRNA and reveals the combined VEGFR-1/VEGFR-2 protein expression as a potentially favorable prognosticator, which merits further evaluation in larger studies.
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- 2015
40. Independent Risk Factors for Anemia in Cancer Patients Receiving Chemotherapy: Results from the European Cancer Anaemia Survey
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Paris Kosmidis, Gunnar Birgegård, Pere Gascón, Maciej Krzakowski, Gail Kongable, Peter Barrett-Lee, Carsten Bokemeyer, Dirk Schrijvers, Maurice Schneider, Simon Van Belle, Heinz Ludwig, and Johan W.R. Nortier
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Anemia ,Colorectal cancer ,medicine.medical_treatment ,Predictive Value of Tests ,Risk Factors ,Neoplasms ,Surveys and Questionnaires ,Internal medicine ,Epidemiology ,medicine ,Humans ,Risk factor ,Aged ,Anemia, Hypochromic ,Chemotherapy ,Evidence-Based Medicine ,Models, Statistical ,Framingham Risk Score ,business.industry ,Incidence ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Europe ,Logistic Models ,ROC Curve ,Oncology ,Area Under Curve ,Predictive value of tests ,Female ,business - Abstract
Objectives: To develop a hitherto unavailable risk factor model for accurately predicting anemia development in cancer patients before chemotherapy (CT) administration. Methods: 2,070 nonanemic patients from the European Cancer Anaemia Survey (ECAS) with hemoglobin (Hb) ≧12 g/dl at enrollment who received their first CT during ECAS and underwent at least two CT cycles were divided randomly into split half (SH) 1 and SH2 (n = 1,035 each). The model was developed on SH1 using logistic regression to simultaneously evaluate predictive factors, and was validated using SH2 and an additional similar subpopulation of 5,901 ECAS patients. Anemia risk values were assigned to the predictive factors and the sum of the predictive factors gave the total anemia risk score; lower-, higher-, and highest-risk cutoff points of the total anemia risk score were determined. Results: Variables ultimately identified as significant predictive factors for anemia were: lower initial Hb (≤12.9 g/dl in females, and ≤13.4 g/dl in males); having lung or gynecologic cancer versus gastrointestinal (GI)/colorectal cancer; cancer at any other site versus GI/colorectal cancer; treatment with platinum CT, and female gender. Conclusion: Using this evidence-based risk model, nonanemic patients who are at the highest risk of develop ing anemia prior to receiving CT can be identified clinically, allowing appropriate anemia management to be planned.
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- 2006
41. Anemia profiles in patients with lung cancer: What have we learned from the European Cancer Anaemia Survey (ECAS)?
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Maciej Krzakowski and Paris Kosmidis
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Anemia ,medicine.medical_treatment ,Population ,Platinum Compounds ,World Health Organization ,Severity of Illness Index ,Hemoglobins ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Prevalence ,Humans ,Medicine ,Prospective Studies ,Lung cancer ,education ,Prospective cohort study ,Aged ,Aged, 80 and over ,education.field_of_study ,Chemotherapy ,business.industry ,Incidence ,Epoetin alfa ,Cancer ,Middle Aged ,medicine.disease ,Surgery ,Europe ,Radiation therapy ,Cross-Sectional Studies ,Oncology ,Data Interpretation, Statistical ,Female ,business ,medicine.drug - Abstract
The often-aggressive therapy, including platinum-based regimens, required to treat lung cancer patients results in a significant risk for anemia in this population. Results of the recent European Cancer Anaemia Survey (ECAS) showed that, at enrollment, 37.6% (753/2002) of lung cancer patients were anemic; rates by cancer treatment were 50.0% on concomitant chemotherapy/radiotherapy, 39.0% on chemotherapy, 31.7% on radiotherapy, 38.6% on combination treatment, and 30.7%, on no treatment. At enrollment, of 605 patients receiving platinum therapy, 50.1% were anemic versus 30.6% of 1252 receiving nonplatinum regimens. During ECAS, 83.3% of lung cancer patients who received chemotherapy were anemic at some time, with the prevalence of anemia in platinum-treated patients increasing progressively from 23.5% at Cycle 1 to 77.3% at Cycle 6 (corresponding values for nonplatinum-treated patients, 32.9% and 57.7%). However, only 47% of anemic patients received anemia treatment, which, when provided, often was not initiated until hemoglobin (Hb) levels were relatively low (initiation Hb: epoetin, 9.1 g/dL; transfusion, 8.5 g/dL). Logistical analysis of ECAS data identified treatment with platinum, female sex, and initial Hb level as risk factors for anemia in lung cancer patients. Given the potential adverse consequences of anemia in lung cancer patients, including diminished quality of life (QOL), it is advisable that treatment patterns for anemia management, especially in regard to anemia monitoring and Hb level used to initiate treatment, be reviewed and optimized, with the goal of optimizing overall patient care. Also, anemia risk factors should be considered, which may help clinicians identify lung cancer patients particularly at risk for this problem, allowing the planning and initiation of appropriate treatment for effective and timely anemia management, thus preserving patient QOL.
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- 2005
42. Consensus on medical treatment of non-small-cell lung cancer—update 2004
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Nick Thatcher, Ch. Manegold, Maciej Krzakowski, Jacek Jassem, Christoph C. Zielinski, S. Tomek, T. Beinert, Fred R. Hirsch, Jeffrey Crawford, J.L. Pujol, Paris Kosmidis, Vassilis Georgoulias, Ch. Herold, N. van Zandwijk, C. Gridelli, Michael Krainer, J.R. Fischer, Robert Pirker, Matjaz Zwitter, and Sabine Zöchbauer-Müller
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Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Medical treatment ,business.industry ,Internal medicine ,medicine ,Non small cell ,Lung cancer ,medicine.disease ,business - Published
- 2005
43. The multidisciplinary rectal cancer treatment: Main convergences, controversial aspects and investigational areas which support the need for an European Consensus
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Bengt Glimelius, Hanry Bartelink, Paolo Latini, Bruce D. Minsky, Paris Kosmidis, Aurelio Picciocchi, Joel E. Tepper, Numa Cellini, Regina G. H. Beets-Tan, Jean Pierre Gerard, Phil Quirke, Lars Påhlman, Vincenzo Valentini, Cornelius Van de Velde, Maurizio Tonato, and Eric Van Cutsem
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medicine.medical_specialty ,Colorectal cancer ,International Cooperation ,Endoscopy, Gastrointestinal ,FOLFOX ,Endoanal ultrasound ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Practice Patterns, Physicians' ,Stage (cooking) ,Neoplasm Staging ,Barium enema ,medicine.diagnostic_test ,Rectal Neoplasms ,business.industry ,Patient Selection ,General surgery ,Hematology ,Rectal examination ,medicine.disease ,Magnetic Resonance Imaging ,Surgery ,Oncology ,Chemotherapy, Adjuvant ,Health Care Surveys ,FOLFIRI ,Radiotherapy, Adjuvant ,business ,Chemoradiotherapy ,medicine.drug - Abstract
Background and purpose During the past decades staging and treatment of rectal cancer are used different in Europe and in North America. To promote a process to integrate the daily practice with the best evidence of the literature an International Conference was organized in Italy. Agreement between Experts, Centres, and specialists who participated in the Conference are reported. Methods Five aspects were analyzed and a questionnaire was tailored for this purpose. The questionnaire had 159 questions. During the Conference, at the beginning of each Session, the moderators showed the answers from the Experts and the Centres, and, at the end of the session, the audience voted in all controversial issues. Agreements were scored at three levels: minimum, if it was between 51 and 74% of votes for each group; moderate, between 75 and 94%; large, more than 94%. Results The main results are: staging : endoanal ultrasound was considered as mandatory in T staging, in the evaluation of sphincter infiltration, and in the restaging of T after chemoradiotherapy (chRT). Magnetic Resonance Imaging is mandatory in the evaluation of mesorectal fascia infiltration. Endoscopy had a moderate agreement for the definition of tumour location, and the barium enema as optional. Digital rectal examination is complementary for staging and PET-CT investigational for T, N and yT staging. Preoperative radiotherapy : for T4 stage chRT was always the preferred treatment, often with moderate agreement, for any tumour location and N status. For T3, chRT received the same agreement except for high location and N0-N1. For T2 stage, N2 and positive nodes outside the mesorectum, chRT received minimum agreement for low and middle tumours; for high tumours only positive nodes outside the mesorectum was agreed upon. Preoperative radiotherapy, negative specimen and sphincter preservation : chRT was agreed by many for all T stages and N presentations of lower third tumours, except for T1-2 N0-N1. Postoperative treatments : the selection for these treatments often received moderate agreement according to the infiltration of surrounding organs, positive nodal status and circumferential radial margins. Therapy of metastatic disease : an agreement was found for FOLFOX as first-line therapy and for FOLFIRI as second-line, although comparaitive studies show similar activity of FOLFOX and FOLFIRI regimens. Conclusions This process represents an expertise opinion process that may contribute to increased scientific debate and to promote the development of ‘guidelines', ‘clinical recommendations' and ultimately a Consensus on the evolving approach to rectal cancer treatment.
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- 2005
44. The European Cancer Anaemia Survey (ECAS): A large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients
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Patrizia Olmi, Peter Barrett-Lee, Pere Gascón, Gunnar Birgegård, Maciej Krzakowski, Dirk Schrijvers, Carsten Bokemeyer, Maurice Schneider, Heinz Ludwig, Simon Van Belle, Paris Kosmidis, and Johan W.R. Nortier
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Adult ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Anemia ,Hemoglobins ,Quality of life ,Neoplasms ,hemic and lymphatic diseases ,Internal medicine ,Prevalence ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Aged ,Aged, 80 and over ,Epoetin beta ,Performance status ,business.industry ,Incidence ,Incidence (epidemiology) ,Cancer ,Middle Aged ,medicine.disease ,Europe ,Prevalence incidence ,Oncology ,Quality of Life ,business - Abstract
The European Cancer Anaemia Survey (ECAS) was conducted to prospectively evaluate the prevalence, incidence and treatment of anaemia (haemoglobin
- Published
- 2004
45. Second Line Chemotherapy with 5 Fluorouracil and Vinorelbine in Anthracycline and Taxane Pretreated Patients with Metastatic Breast Cancer
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Paris Kosmidis, George Fountzilas, Jim Janinis, Christos Christodoulou, Charalambos Bakoyiannis, Helen Timotheadou, Evangelia Razis, and Gerassimos Aravantinos
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,Phases of clinical research ,Breast Neoplasms ,Vinblastine ,Vinorelbine ,Folinic acid ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,Infusions, Intravenous ,Aged ,Salvage Therapy ,Taxane ,business.industry ,General Medicine ,Middle Aged ,Evaluable Disease ,medicine.disease ,Survival Analysis ,Metastatic breast cancer ,Treatment Outcome ,Drug Resistance, Neoplasm ,Fluorouracil ,Injections, Intravenous ,Female ,business ,medicine.drug - Abstract
5-Fluorouracil (5-FU) and Vinorelbine (Vin) are active in the second line therapy of metastatic breast cancer (MBC). We conducted a multi-institutional phase II study to assess the activity of the combination of 5-FU and Vin in anthracycline and taxane pretreated patients with MBC.Patients with MBC previously treated with anthracyclines and taxanes, who had measurable or evaluable disease, were treated with folinic acid 200 mg/m2 IV, 5-FU 400 mg/m2 IV bolus, and 5-FU 600 mg/m2 continuous infusion over 24 hours on days 1, 2, 15, and 16 and Vin 25 mg/m2 on days 1 and 15 of a 28-day cycle, for six cycles. Response rate, time to disease progression, overall survival, and toxicity were evaluated.Thirty-eight patients were enrolled and 35 were evaluable for response. Grade III and IV neutropenia was seen in four and three patients, respectively. At a median follow-up of 19.5 months, 33 patients have progressed, 14 during treatment and 19 during the follow-up period, and 23 have died for an overall survival of 12.3 months. The time to progression was six months. Eight patients had a partial response and 14 had stable disease for a clinical benefit rate of 63%.The combination of 5-FU and Vin is well tolerated and is a good option for the palliative care of patients with MBC.
- Published
- 2004
46. Chemotherapy in NSCLC: historical review
- Author
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Paris Kosmidis
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Palliative care ,medicine.medical_treatment ,Disease ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,medicine ,Humans ,Combined Modality Therapy ,In patient ,Etoposide ,Randomized Controlled Trials as Topic ,Chemotherapy ,business.industry ,Gold standard ,History, 20th Century ,medicine.disease ,Surgery ,Cisplatin ,business ,Median survival - Abstract
The use of chemotherapy in patients with advanced NSCLC has been under investigation for several years. It has evolved from administration in the palliative care setting to integration into combined-modality curative therapy settings in patients with locoregionally-advanced disease. Following the largest meta-analysis in 1995 it was suggested that platinum-based chemotherapy was effective in treating patients with advanced disease. The absolute improvement in survival was 10% at 1 year and an increased median survival of 1.5 months. Since this analysis, platinum-based chemotherapy is considered the gold standard of treatment in this disease.
- Published
- 2002
47. Protein expression patterns of cell cycle regulators in operable breast cancer
- Author
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Christos Christodoulou, George C. Zografos, Flora Zagouri, George Fountzilas, Sofia Chrisafi, Charisios Karanikiotis, George Pentheroudakis, Georgios Lazaridis, Triantafyllia Koletsa, Maria Sotiropoulou, P. Skarlos, Vassiliki Kotoula, Gerasimos Aravantinos, Pavlos Papakostas, Angelos Koutras, Mattheos Bobos, Christos Valavanis, Helen Trihia, Theofani Gavressea, Niki Arnogiannaki, Paris Kosmidis, George Kouvatseas, Dimitrios Bafaloukos, and Christos Papadimitriou
- Subjects
0301 basic medicine ,Oncology ,Protein Expression ,Cancer Treatment ,lcsh:Medicine ,Triple Negative Breast Neoplasms ,0302 clinical medicine ,Breast Tumors ,Medicine and Health Sciences ,Cyclin D1 ,Cell Cycle and Cell Division ,Breast ,lcsh:Science ,Cyclin ,Oncogene Proteins ,Multidisciplinary ,Middle Aged ,Cell cycle ,Prognosis ,Immunohistochemistry ,Cell Processes ,030220 oncology & carcinogenesis ,Female ,Anatomy ,Cyclin-Dependent Kinase Inhibitor p27 ,Research Article ,Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,medicine.medical_specialty ,Histology ,Antineoplastic Agents ,Breast Neoplasms ,Context (language use) ,Biology ,Research and Analysis Methods ,Young Adult ,03 medical and health sciences ,Breast cancer ,Diagnostic Medicine ,Cyclins ,Internal medicine ,Breast Cancer ,Cyclin E ,Gene Expression and Vector Techniques ,medicine ,Humans ,Molecular Biology Techniques ,Molecular Biology ,Immunohistochemistry Techniques ,Survival analysis ,Aged ,Molecular Biology Assays and Analysis Techniques ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Cell Biology ,medicine.disease ,Survival Analysis ,Histochemistry and Cytochemistry Techniques ,Cyclin E1 ,030104 developmental biology ,Immunologic Techniques ,lcsh:Q ,Tumor Suppressor Protein p53 - Abstract
Background-Aim To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. Methods Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis. Results Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1, whereas ER-positive tumors did not. Absence of Cyclin D1 predicted for worse OS, while absence of Cyclin E1 for poorer DFS. The expression patterns of all examined proteins yielded 3 distinct clusters; (1) Cyclin D1 and/or E1 positive with moderate p21 expression; (2) Cyclin D1 and/or E1, and p27 positive, p53 protein negative; and, (3) Cyclin D1 or E1 positive, p53 positive, p21 and p27 negative or moderately positive. The 5-year DFS rates for clusters 1, 2 and 3 were 70.0%, 79.1%, 67.4% and OS 88.4%, 90.4%, 78.9%, respectively. Conclusions It seems that the expression of cell cycle regulators in the absence of p53 protein is associated with favorable prognosis in operable breast cancer.
- Published
- 2017
48. Docetaxel and intermittent erlotinib in patients with metastatic Non-Small Cell Lung Cancer; a phase II study from the Hellenic Cooperative Oncology Group
- Author
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Vasilios, Karavasilis, Paris, Kosmidis, Konstantinos N, Syrigos, Polyxeni, Mavropoulou, Meletios A, Dimopoulos, Vassiliki, Kotoula, Dimitrios, Pectasides, Ioannis, Boukovinas, George, Klouvas, Anna, Kalogera-Fountzila, Christos N, Papandreou, George, Fountzilas, and Evangelos, Briasoulis
- Subjects
Adult ,Male ,Lung Neoplasms ,Docetaxel ,Middle Aged ,Erlotinib Hydrochloride ,Treatment Outcome ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Quinazolines ,Humans ,Female ,Taxoids ,Neoplasm Grading ,Neoplasm Metastasis ,Aged - Abstract
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 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).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).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.
- Published
- 2014
49. Intact or broken-apart RNA: an alternative concept for ALK fusion screening in non-small cell lung cancer (NSCLC)
- Author
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George Fountzilas, Larisa V. Debelenko, Sofia Chrisafi, Vassiliki Kotoula, Eleftheria Tsolaki, Amanda Psyrri, Kyriaki Papadopoulou, Paris Kosmidis, Catherine Michail-Strantzia, Maria Vassilakopoulou, George Lazaridis, Ioannis Efstratiou, and Mattheos Bobos
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Histology ,Lung Neoplasms ,Oncogene Proteins, Fusion ,Pyridines ,non-small cell lung cancer (NSCLC) ,Antineoplastic Agents ,In situ hybridization ,Biology ,Translocation, Genetic ,Pathology and Forensic Medicine ,Crizotinib ,Predictive Value of Tests ,hemic and lymphatic diseases ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,RNA, Messenger ,Diagnostic Errors ,Survival analysis ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Messenger RNA ,RNA ,Receptor Protein-Tyrosine Kinases ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Survival Analysis ,Medical Laboratory Technology ,Cancer research ,Pyrazoles ,Female ,medicine.drug - Abstract
Anaplastic lymphoma kinase (ALK) break-apart fluorescent in situ hybridization (FISH) is currently used in diagnostics for the selection of non-small cell lung cancer (NSCLC) patients to receive crizotinib. We evaluated ALK status in NSCLC with a novel ALK mRNA test based on the break-apart FISH concept, which we called break-apart transcript (BAT) test. ALK5' and ALK3' transcript patterns were established with qPCR for ALK-expressing controls including fusion-negative neuroblastomas, as well as fusion-positive anaplastic large cell lymphomas and NSCLC. The BAT test was evaluated on 271 RNA samples from routinely processed paraffin NSCLC tissues. Test results were compared with ALK FISH (n=121), immunohistochemical (IHC) analysis (n=86), and automated quantitative analysis (AQUA, n=83). On the basis of the nonoverlapping ALK BAT patterns in ALK-expressing controls (P0.0001), 8/174 adenocarcinomas (4.6%) among 259 informative NSCLC were predicted as fusion positive. Overall concordance for paired method results was high (94.1% to 98.8%) but mainly concerned negative prediction because of the limited availability of positive-matched cases. Tumors with 100% cytoplasmic IHC staining of any intensity (n=3) were positive for AQUA, FISH, and BAT test; tumors with lower IHC positivity and different staining patterns were AQUA-negative. Upon multiple reevaluations, ALK gene status was considered as originally misinterpreted by FISH in 3/121 cases (2.5%). Tumors with4 ALK gene copies were associated with longer overall survival upon first-line chemotherapy. In conclusion, application of the ALK BAT test on routinely processed NSCLC tissues yields the same fusion partner independent information as ALK break-apart FISH but is more robust and cost-effective. The BAT concept may be considered for the development of further drug-predictive translocation tests.
- Published
- 2014
50. A Randomized Open-Label Parallel-Group Study Comparing Ondansetron with Ondansetron plus Dexamethasone in Patients with Metastatic Breast Cancer Receiving High-Dose Epirubicin. A Hellenic Cooperative Oncology Group Study
- Author
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Dimitrios Bafaloukos, Jim Janinis, George Fountzilas, Dimosthenis Skarlos, Athanasios Athanasiades, Kostas Nikolaides, Paris Kosmidis, Theodore Giannakakis, and Nicholas Pavlidis
- Subjects
Cancer Research ,Antiemetics/*therapeutic use ,Vomiting ,Nausea ,medicine.medical_treatment ,Breast Neoplasms ,Serotonin Antagonists/*therapeutic use ,Dexamethasone ,030218 nuclear medicine & medical imaging ,Ondansetron ,03 medical and health sciences ,Ondansetron/administration & dosage/*therapeutic use ,0302 clinical medicine ,Vomiting/*prevention & control ,medicine ,Humans ,Retching ,Adverse effect ,Epirubicin ,Dexamethasone/*administration & dosage ,Chemotherapy ,Antibiotics, Antineoplastic ,business.industry ,Breast Neoplasms/*drug therapy ,Epirubicin/*adverse effects ,General Medicine ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Anesthesia ,Antiemetics ,Drug Therapy, Combination ,Female ,Serotonin Antagonists ,medicine.symptom ,Antibiotics, Antineoplastic/*adverse effects ,business ,medicine.drug - Abstract
Aims and background The purpose of this multicenter randomized, open-label, parallel-group study was to assess whether the addition of low-dose dexamethasone to ondansetron results in improved control of chemotherapy-induced emesis in patients undergoing first-line chemotherapy with high-dose epirubicin. Methods & study design Patients were randomized to receive either 24 mg of ondansetron or 24 mg of ondansetron plus 8 mg of dexamethasone administered as an intravenous infusion 30 minutes prior to administration of chemotherapy. Both groups of patients received 8 mg of ondansetron given orally from day 2 to 5 two times daily. Fifty-three patients received ondansetron and 50 received ondansetron plus dexamethasone. The patients recorded nausea and the number of vomits and retches daily on diary cards. Results Significantly more patients in the ondansetron plus dexamethasone group experienced neither vomiting nor retching during the first day of the first course of chemotherapy compared to those receiving ondansetron alone (79.6% vs 53.8%, P = 0.0062). Furthermore, there was a trend in favor of ondansetron plus dexamethasone in the control of nausea. There was no statistically significant difference between ondansetron plus dexamethasone versus ondansetron alone in protecting patients from emesis between days 2 and 5 of the first course of chemotherapy (66.7% vs 62.7%, P = 0.68). This was probably due to the small sample size. Ondansetron was well tolerated, with 15 patients (15%) reporting adverse events such as headache or constipation. Conclusions It appears that ondansetron given intravenously in combination with dexamethasone is more effective than ondansetron alone in the control of acute emesis in patients undergoing their first course of chemotherapy with high-dose epirubicin. No difference between the regimens was found with regard to nausea and delayed emesis control.
- Published
- 2000
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