A Psyrri

Attikon University Hospital, Athínai, Attica, Greece

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Publications (54)276.99 Total impact

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    ABSTRACT: Background: Plasma fibrinogen may be involved in several stages of cancer progression. Clinical studies have demonstrated that pretreatment plasma fibrinogen is associated with poor survival in various cancers. The aim of this meta-analysis was to examine the prognostic effect of circulating fibrinogen in solid tumors. Materials and methods: We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, and meeting proceedings to identify studies assessing the effect of pretreatment plasma fibrinogen on survival of cancer patients. Pooled multivariable-adjusted hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were estimated using random-effects models. Results: Data from 52 observational studies and 15,371 patients were summarized. An elevated baseline plasma fibrinogen was significantly associated with worse OS (pooled HR=1.69; 95% CI=1.48-1.92). The highest negative effect of elevated plasma fibrinogen on OS was demonstrated in renal cell carcinoma (pooled HR=2.22), followed by head and neck cancer (pooled HR=2.02), and colorectal cancer (pooled HR=1.89). The adverse prognostic impact of high plasma fibrinogen remained in both non-metastatic and metastatic disease and patients of different ethnicity. Patients with high baseline fibrinogen had a significantly shorter DFS (pooled HR=1.52) and CSS (pooled HR=2.50). Conclusions: An elevated pretreatment plasma fibrinogen significantly correlates with decreased survival in patients with solid tumors. Future clinical trials are warranted to determine whether plasma fibrinogen could be incorporated in cancer staging systems and whether fibrinogen-lowering therapies have a favorable effect on disease recurrence and mortality.
    No preview · Article · Oct 2015 · Cancer Treatment Reviews
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    ABSTRACT: The adenocarcinoma subtype of non-small cell lung cancer (adeno-NSCLC) is routinely treated with chemotherapy if patients do not have molecular aberrations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements. There are currently no validated biomarkers that can predict if patients will gain clinical benefit from chemotherapy, leading to a majority of patients receiving many cycles of unnecessary chemotherapy. We hypothesized that the percentage rise in plasma caspase-cleaved cytokeratin 18 (cCK18) and total cytokeratin 18 (tCK18) assessed before and after chemotherapy correlates with the radiological response to chemotherapy. Plasma samples from 40 patients with stage IV adeno-NSCLC, treated with first-line chemotherapy with carboplatin (AUC5) plus pemetrexed (500 mg/m(2)), were collected prior to chemotherapy and 48 h after treatment. ELISA was used to quantify cCK18 and tCK18. The male-to-female ratio was 3:1, and the median age of patients was 63 years. Patients who had a clinical benefit (complete response, partial response or stable disease) at the first radiological assessment following chemotherapy had a significantly higher percentage change in plasma tCK18 levels compared to those who had no clinical benefit, i.e. progressive disease (69.5 ± 75.1 vs. 25.3 ± 30.9%, respectively; p = 0.042). The receiver operating characteristic area was 0.712 (p = 0.039). There was an increase in the percentage change in cCK18 in patients with clinical benefit compared to those without clinical benefit but this was not statistically significant (57.6 ± 112.8 vs. 24.38 ± 45.1%, respectively; p = 0.85). The percentage change in plasma tCK18 levels before and after the first cycle of pemetrexed and carboplatin chemotherapy is associated with clinical benefit. If validated in larger cohorts, this test can be used to identify patients unlikely to respond to treatment who can thus be offered alternative treatments or entry into clinical trials. © 2015 S. Karger AG, Basel.
    No preview · Article · Feb 2015 · Oncology
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    ABSTRACT: We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC). The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan-Meier curves and Cox regression models were used for survival analyses. A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders (p=0.032 and p=0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival (p=0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients. Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.
    No preview · Article · Dec 2014 · Oral Oncology
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    ABSTRACT: Abstract AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions
    Full-text · Article · Nov 2014
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    ABSTRACT: Approximately 5-10% of breast cancer cases might be inheritable, up to 30% of which are due to BRCA1/2 mutations. During the past few years and thanks to technology evolution, we have been witnesses of an intensive search of additional genes with similar characteristics, under the premise that successful gene discovery will provide substantial opportunities for primary and secondary prevention of breast cancer. Consequently, new genes have emerged as breast cancer susceptibility genes, including rare germline mutations in high penetrant genes, such as TP53 and PTEN, and more frequent mutations in moderate penetrant genes, such as CHEK2, ATM and PALB2. This review will summarize current data on new findings in breast cancer susceptibility genes.
    No preview · Article · Nov 2014 · Cancer Treatment Reviews
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    ABSTRACT: Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I-IV in relation to clinicopathological features. Increased p-AKT expression correlated with poor prognosis in plaques (P=0.0198), whereas p-AKT was an independent predictor of poor survival in the entire cohort (P=0.017, HR=1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P=0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P=0.0253) and progression (P<0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients' prognosis with tumours.
    No preview · Article · Sep 2014 · Experimental Dermatology
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    ABSTRACT: Background: Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial. Methods: Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130). Results: Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28–3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073). Conclusions: High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy.
    Full-text · Article · Aug 2014 · British Journal of Cancer
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    A Psyrri · T Rampias · J B Vermorken
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    ABSTRACT: Background: Squamous cell carcinoma of the head and neck (SCCHN) was traditionally associated with smoking and alcohol use; however, human papillomavirus (HPV) infection has recently been implicated as a novel risk factor for oropharyngeal tumors. Furthermore, HPV-associated oropharyngeal carcinoma (OPC) appears to be a distinct entity with different epidemiology, biology, and clinical outcomes. Methods: Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in both the locoregionally advanced (LA) and recurrent/metastatic (RM) disease setting and discuss ongoing trials that may eventually impact the treatment of patients with HPV-positive (HPV+) SCCHN. Results: A body of retrospective and prospective data established an association between HPV+ OPC and better survival, particularly for LA disease. Current data on RM disease are limited, but they also suggest prognostic significance for HPV. Conclusions: Better outcomes in HPV+ LA disease may allow for less aggressive treatment in the future, and several trials are evaluating deintensified regimens in patients with HPV+, LA OPC; it should be emphasized that deintensification strategies are appropriate only in a clinical research setting and only for selected subgroups of HPV+ patients. In addition, HPV-targeted strategies, such as vaccines, are currently undergoing clinical evaluation. On the other hand, the prognostic impact of HPV in RM disease requires further validation before any modifications in treatment can be made. Likewise, the predictive significance of HPV status in both disease settings remains to be defined. Clinical trial numbers: NCT00226239, NCT00301028, NCT00387127, NCT00410826, NCT00503997, NCT00514943, NCT00544414, NCT00768664, NCT00939627, NCT01084083, NCT01302834, NCT01687413, NCT01706939.
    Full-text · Article · Jul 2014 · Annals of Oncology
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    G Mountzios · T Rampias · A Psyrri
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    ABSTRACT: Squamous-cell cancer of the head and neck (SCCHN) represents a heterogeneous disease entity, with various etiological factors implicated in the genesis of distinct molecular subsets of tumors, which exhibit different biological and clinical behavior. Treatment of SCCHN is expected to change in the next decade as targeted therapies continue to make strides. Recently, next-generation sequencing studies conducted on ∼190 SCCHN specimens shed light into the molecular pathogenesis of the disease. These studies discovered mutations in genes involved in the differentiation program of squamous epithelium and the Notch/p63 axis (such as NOTCH1, TP63 and FBXW7), and validated genetic alterations derived from previous studies (such as mutations in TP53, CDKN2A, PIK3CA, CCND1 and HRAS) as driver genetic events in SCCHN neoplastic transformation. More recently, comprehensive data from The Cancer Genome Atlas (TCGA) project on 306 SCCHN specimens provided further insight into SCCHN inherent molecular complexity, identifying novel significantly mutated genes, including FAT1, MLL2, TGFRBR2, HLA-A, NFE2l2 and CASP8. In this article, we provide an overview of the mutational spectrum of SCCHN, with emphasis on the clinical implementation of this knowledge. We also discuss the potential integration of new data within the framework of precision cancer medicine. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected] /* */
    Full-text · Article · Apr 2014 · Annals of Oncology
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    ABSTRACT: Tumor human papillomavirus (HPV) status is an important prognostic factor in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Prognostic value in recurrent and/or metastatic (R/M) disease remains to be confirmed. This retrospective analysis of the EXTREME trial, comparing chemotherapy plus cetuximab with chemotherapy first line in R/M SCCHN, investigated efficacy and prognosis according to tumor p16 and HPV status. Paired tissue samples were used: p16INK4A expression was assessed by immunohistochemistry, and HPV status determined in extracted DNA samples using oligonucleotide hybridization assays. Altogether, 416 of 442 patients had tumor samples available for p16 and HPV: 10% of tumors were p16 positive and 5% were HPV positive. Adding cetuximab to chemotherapy improved survival, irrespective of tumor p16 or HPV status. This pattern remained in a combined analysis of p16 and HPV. p16 positivity and HPV positivity were associated with prolonged survival compared with p16 negativity and HPV negativity. Subgroup analysis of patients with oropharyngeal cancer demonstrated a similar pattern to all evaluable patients. The results from this analysis suggest that p16 and HPV status have prognostic value in R/M SCCHN and survival benefits of chemotherapy plus cetuximab over chemotherapy alone are independent of tumor p16 and HPV status.
    Full-text · Article · Feb 2014 · Annals of Oncology

  • No preview · Article · Jan 2014 · Molecular Cancer Therapeutics
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a challenging cancer to treat and cure. A great proportion of patients present with advanced disease and appropriate treatment options include surgical resection with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT), radical concurrent CRT or RT with monoclonal antibody cetuximab. Despite improved outcomes with CRT, overall prognosis is still unsatisfactory and treatment-related toxicity is a matter of major importance. To obtain improved outcomes and mitigate disease recurrence, current research is focused on novel molecular targeted agents, immunotherapy and discovery of predictive markers. Herein, we summarise recent advances in treatment of head and neck cancer, as presented in European Society for Medical Oncology (ESMO) Congress 2014.
    No preview · Article · Jan 2014 · European Oncology and Haematology

  • No preview · Article · May 2013
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    ABSTRACT: Background: In this report, we investigated the prognostic value of the cell cycle analysis parameters of patients with unresectable locally advanced head and neck squamous carcinoma treated with two different radiotherapy regimens. The secondary endpoint was the evaluation of quality of life before and after radiotherapy in both schedules. Methods: Twenty two patients were randomized to receive either conventional (70 Gy/2 Gy/fr) or accelerated (64.4 Gy/2.3Gy/fr) 3-D Conformal RT. A fine-needle aspiration (FNA) of the primary or gross adenopathy combined with flow cytometry was carried out before any treatment. QLQ-H&N35 questionnaire was assessed in all patients, performed at baseline and a week after radiotherapy. Results: Finally, specimens from only nine patients were eligible for flow cytometry. The spearman rho correlation showed no statistical significance between the expression malignant cells in the different cell cycle phases and overall survival, except a trend in S phase (rho= -0.54, P=0.088). A significant (p < 0.05, Wilcoxon test) better outcome (pre vs post-RT) was observed in the scales of global QoL H&N 35 at 29 out of the 35 scales in both RT schedules. No statistical difference was found in QoL H&N 35 scales for conventional versus accelerated schedule of radiotherapy (P>0.05, Mann Whitney test). No difference in survival was noted between the two groups (P=0.92, log-rank test). Acute and late radiation induced toxicity was also equivalent in both schedules. Conclusions: This study identified that both radiotherapy arms were equivalent in terms of QoL and toxicity. The number of cells in S phase correlated negatively but not-significantly with overall survival. A statistical significant improvement of quality of life was observed one month after the end of irradiation in both arms. More patients with eligible for analysis specimens are needed for the extraction of safe results.
    Full-text · Article · Apr 2013 · Head & Neck Oncology
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    ABSTRACT: Background We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16(+) oropharyngeal cancer cells.MethodsHPV16(+) and HPV(-) HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH).ResultsIn HPV16(+) cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPV(+)/p16(+) tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and β-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16(-)/HPV(-) patients, 11.63 for p16(-)/HPV(+) patients and was not reached for p16(+)/HPV(-) and p16(+)/HPV(+) groups.Conclusions Aberrant EGFR signaling contributes to malignant conversion of HPV16(+) HNSCC cells. These results validate β-catenin as a distinct biomarker in HPV(+)/p16(+) HNSCC. Wnt signaling inhibitors merit exploration in HPV(+)/p16(+) HNSCC.
    Full-text · Article · Feb 2013 · Annals of Oncology

  • No preview · Article · Dec 2012 · Cancer Research
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    ABSTRACT: Background The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.Patients and methodsOne hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).ResultsThe median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).Conclusions Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population.Clinical Trial NumberACTRN12610000845033, www.anzctr.org.au.
    Full-text · Article · Nov 2012 · Annals of Oncology

  • No preview · Article · Sep 2012 · Annals of Oncology
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    ABSTRACT: Background We evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, by comparing PRT with CRT in pts with LASCCHN.
    Full-text · Article · Sep 2012 · Annals of Oncology
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    ABSTRACT: Objective: The hepatocellular carcinoma-related protein 1 (HCRP1) is a key factor in the degradation of the epidermal growth factor receptor. In this study, we assessed the prognostic significance of HCRP1 expression in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods: HCRP1 expression was determined by immunohistochemistry on tissue biopsy sections of 111 patients with locally advanced OOSCC undergoing neoadjuvant chemoradiotherapy followed by surgery. The Kaplan-Meier method and Cox regression models were used for survival analyses. Results: Low HCRP1 expression was associated with poor recurrence-free survival (P = 0.046) and overall survival (P = 0.03). Multivariate analysis revealed that low HCRP1 expression remained an independent risk factor for relapse (HR 2.98, 95% CI 1.19-7.49, P = 0.02) and death (HR 3.04, 95% CI 1.19-7.79, P = 0.02). Conclusion: Low HCRP1 expression was found to be of adverse prognostic significance in patients with OOSCC who received preoperative chemoradiotherapy.
    No preview · Article · Jul 2012 · Oral Diseases

Publication Stats

732 Citations
276.99 Total Impact Points

Institutions

  • 2007-2015
    • Attikon University Hospital
      • Department of Internal Medicine IV
      Athínai, Attica, Greece
  • 2012-2014
    • National and Kapodistrian University of Athens
      • Division of Internal Medicine V
      Athínai, Attica, Greece
  • 2004-2014
    • Yale University
      New Haven, Connecticut, United States
  • 2000-2007
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 1999
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States