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Valachis A.,Onkologkliniken Sormland | Mauri D.,PACMeR | Mauri D.,General Hospital | Neophytou C.,PACMeR | And 5 more authors.
International Journal of Medical Sciences | Year: 2011

Background: The number of genetic association studies is increasing exponentially. Nonetheless, genetic association reports are prone to potential biases which may influence the reported outcome. Aim: We hypothesized that positive outcome for a determined polymorphism might be over-reported across genetic association studies analysing a small number of polymorphisms, when compared to studies analysing the same polymorphism together with a high number of other polymorphisms. Methods: We systematically reviewed published reports on the association of glutathione s-transferase (GST) single-nucleotide polymorphisms (SNPs) and cancer outcome. Result: We identified 79 eligible trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies an-alysing one to three polymorphisms (n = 39) were significantly more likely to present positive outcomes, compared to studies examining more than 3 polymorphisms (n=40) p = 0.004; this was particularly evident for studies analysing the GSTM1polymorphism (p =0.001). We found no significant associations between journal impact factor, number of citations, and probability of publishing positive studies or studies with 1-3 polymorphisms examined. Conclusions: We propose a new subtype of publication bias in genetic association studies. Positive results for genetic association studies analysing a small number of polymorphisms (n = 1-3) should be evaluated extremely cautiously, because a very large number of such studies are inconclusive and statistically under-powered. Indeed, publication of misleading reports may affect harmfully medical decision-making and use of resources, both in clinical and pharmacological development setting. © Ivyspring International Publisher.

Valachis A.,University General Hospital of Heraklion | Mauri D.,PACMeR | Polyzos N.P.,PACMeR | Mavroudis D.,University General Hospital of Heraklion | And 2 more authors.
Breast Journal | Year: 2010

The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast-radiation therapy (WBRT). We conducted a systematic review and meta-analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674-1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506-1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278-7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396-3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058-5.715; p < 0.0001) compared with whole breast-radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast-radiation. Nevertheless the issue of loco-regional recurrence needs to be further addressed.

Valachis A.,University General Hospital of Heraklion | Polyzos N.P.,PACMeR | Polyzos N.P.,University General Hospital of Larisa | Patsopoulos N.A.,Harvard University | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2010

Abstract:: Numerous studies have demonstrated that angiogenesis and in particular VEGF over-expression play an essential role in the progression and metastatic potential of breast cancer. Bevacizumab is a humanized recombinant monoclonal antibody that specifically blocks the binding of VEGF to high-affinity receptors and it has been recently used for the treatment of metastatic breast cancer. We conducted a meta-analysis to synthesize available evidence for use of bevacizumab in metastatic breast cancer patients. Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, progression free survival (PFS) and objective response rate (ORR). Five trials were identified with 3,163 eligible patients. Combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in PFS (HR = 0.70, 95% CI 0.60-0.82, P = 9.3 × 10-6) and ORR (RR = 1.26, 95% CI 1.17-1.37, P = 9.96 × 10-9) compared with chemotherapy alone. Differences in objective response rates were substantial independently by the type of chemotherapy used, while PFS advantages were observed only for taxanes. The pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (HR = 0.90, 95% CI 0.80-1.03, P = 0.119). This meta-analysis shows that the addition of bevacizumab to chemotherapy offers meaningful improvement in PFS and ORR in patients with metastatic breast cancer. Bevacizumab treatment might be suggested for treatment of 1st line metastatic breast cancer, but more data are needed until statistical overall survival differences will be documented and firm guideline recommendation could be given. © 2010 Springer Science+Business Media, LLC.

Karampoiki V.,Panhellenic Association for Continual Medical Research PACMeR | Alevizaki P.,Panhellenic Association for Continual Medical Research PACMeR | Lakiotis V.,Panhellenic Association for Continual Medical Research PACMeR | Loukidou E.,Panhellenic Association for Continual Medical Research PACMeR | And 12 more authors.
Journal of B.U.ON. | Year: 2010

Purpose: Screening is a significant method for cancer control, nevertheless the implementation of non cost-effective screening tests at national level may constitute a major burden to health economics. The purpose of this study was to determine the cancer screening activities of a large sample of the Hellenic population, in a country with opportunistic screening practice. Methods: A large survey on cancer screening in Greece was organized and conducted by the Panhellenic Association for Continual Medical Research (PACMeR). Screening performance of evidence-based (EB), non-evidence-based (non EB) and of undefined benefit tests was analysed. Results: 7001 individuals were analysed. Eighty-eight percent of males and 93% of females stated that they were interested in cancer screening practices. Gynecological cancer screening was performed in the range of 23-38%. Colorectal cancer screening was rarely performed in both genders (1-2%), while non-evidence-based tests were regularly performed (urinalysis 50% and chest radiography 15-18%). Full blood count and PSA measurement were widely accepted (over 45% in both genders and 19.5% in males, respectively). Sociodemographic characteristics did not influence the performance of EB tests in males while females 'activities were highly influenced by such parameters. Conclusion: Opportunistic cancer screening in a primary health care system where national guidelines are missing may cause ambiguous results. Reconsideration of health policy in such cases is mandatory. © 2010 Zerbinis Medical Publications.

Valachis A.,University of Crete | Valachis A.,Central Hospital of Eskilstuna | Mauri D.,PACMeR | Polyzos N.P.,PACMeR | And 3 more authors.
Breast | Year: 2011

Purpose: To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer. Methods: Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity. Results: Five trials were identified with 515 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). No significant difference in terms of breast-conserving surgery between the two treatment arms was observed (OR: 0.98, 95% CI: 0.80-1.19, p-value = 0.82). Regarding toxicity, the addition of trastuzumab did not increase the incidence of neutropenia, neutropenic fever, and cardiac adverse events. Conclusion: The addition of trastuzumab in HER2-positive breast cancer in the neoadjuvant setting improves the probability of achieving higher pCR with no additional toxicity. Based on the available evidence, the use of trastuzumab combined with neoadjuvant chemothetherapy in patients with HER2-positive breast cancer seems to offer substantial benefit in terms of pCR. © 2011 Elsevier Ltd.

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