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  • 1. Gojon, H.
    et al.
    Fawunmi, D.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sentinel lymph node biopsy in patients with microinvasive breast cancer: A systematic review and meta-analysis2014In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 1, p. 5-11Article, review/survey (Refereed)
    Abstract [en]

    Background: The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer. Methods: We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity. Findings: A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%-4.6%), 4.0% (95% CI 2.7%-5.5%), and 2.9% (95% CI: 1.6%-4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate. Interpretation: The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized. (C) 2013 Elsevier Ltd. All rights reserved.

  • 2.
    Kofteridis, Diamantis P.
    et al.
    Univ Hosp Heraklion, Dept Internal Med, Infect Dis Unit, Iraklion 71110, Greece..
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Malarsjukhuset, Dept Oncol, Eskilstuna, Sweden..
    Dimopoulou, Dimitra
    Univ Hosp Heraklion, Dept Internal Med, Infect Dis Unit, Iraklion 71110, Greece..
    Andrianaki, Angeliki M.
    Univ Hosp Heraklion, Dept Internal Med, Infect Dis Unit, Iraklion 71110, Greece..
    Christidou, Athanasia
    Univ Hosp Heraklion, Clin Microbiol, Iraklion 71110, Crete, Greece..
    Maraki, Sofia
    Univ Hosp Heraklion, Clin Microbiol, Iraklion 71110, Crete, Greece..
    Spernovasilis, Nikolaos A.
    Univ Hosp Heraklion, Dept Internal Med, Infect Dis Unit, Iraklion 71110, Greece..
    Samonis, George
    Univ Hosp Heraklion, Dept Internal Med, Infect Dis Unit, Iraklion 71110, Greece..
    Factors Influencing Non-albicans Candidemia: A Case-Case-Control Study2017In: Mycopathologia, ISSN 0301-486X, E-ISSN 1573-0832, Vol. 182, no 7-8, p. 665-672Article in journal (Refereed)
    Abstract [en]

    The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.

  • 3. Matikas, Alexios
    et al.
    Zerdes, Ioannis
    Lovrot, John
    Richard, Francois
    Sotiriou, Christos
    Bergh, Jonas C. S.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Foukakis, Theodoros
    Prognostic implications of PD-L1 expression in breast cancer at the protein and mRNA levels2019In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 15, article id e14284Article in journal (Other academic)
    Abstract [en]

    Background: Conflicting data have been reported on the prognostic value of PD-L1 expression per immunohistochemistry (IHC) in breast cancer (BC). There is a paucity of data on the role of PD-L1 gene expression (GE).

    Methods: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched and data were extracted independently by two researchers. Outcomes included pooled PD-L1 positivity in tumor cells, immune cells or both, per subtype and per antibody used; and the prognostic value of PD-L1 positivity for DFS and OS. Heterogeneity was assessed using the Q and I2 statistics. A pooled GE analysis of 39 publicly available transcriptomic datasets was also performed.

    Results: Of the initial 4184 entries, 38 retrospective studies fulfilled the inclusion criteria. The overall pooled PD-L1 positivity rate in tumor cells was 24%, 33% in immune cells and 25% in both; highest positivity was reported with Dako 28-8 clone. PD-L1 IHC expression in tumor cells was prognostic for shorter DFS (HR = 1.36, 95% CI 1.02 – 1.83, p < 0.04) and OS (HR = 1.66; 95% CI 1.09 – 2.50, p = 0.02); there was significant heterogeneity. PD-L1 IHC expression in immune cells was associated with better DFS (HR = 0.61; 95% CI 0.51 – 0.73, p < 0.001) and OS (HR = 0.53, 95% CI 0.39 – 0.73, p < 0.001) in TNBC. In addition, higher PD-L1 GE predicted better survival in multivariate analysis in the entire population (HR = 0.70, 95% CI 0.60 – 0.82, p < 0.001 for DFS and HR = 0.84, 95% CI 0.75 – 0.93, p = 0.001 for OS) and in basal-like tumors (HR = 0.55, 95% CI 0.38 – 0.80, p = 0.001 for DFS and HR = 0.63, 95% CI 0.50 – 0.79, p < 0.001 for OS), pinteraction 0.124 for DFS and 0.005 for OS.

    Conclusions: The largest to our knowledge meta-analysis on IHC PD-L1 expression in BC informs on PD-L1 positivity rates and its prognostic value. Standardization is needed prior to routine implementation. PD-L1 GE is a promising prognostic factor, especially in basal-like BC.

  • 4.
    Matikas, Alexios
    et al.
    Breast Center, Theme Cancer, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden.
    Zerdes, Ioannis
    Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden.
    Lövrot, John
    Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden.
    Richard, François
    Institute Jules Bordet, Brussels, Belgium.
    Sotiriou, Christos
    Institute Jules Bordet, Brussels, Belgium.
    Bergh, Jonas
    Breast Center, Theme Cancer, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Foukakis, Theodoros
    Breast Center, Theme Cancer, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden.
    Prognostic implications of PD-L1 expression in breast cancer: systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data2019In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 25, no 18, p. 5717-5726Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer.

    EXPERIMENTAL DESIGN: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells or both, per subtype and per antibody used; and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed.

    RESULTS: Of the initial 4184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI 15 - 33%) in tumor cells and 33% (95% CI 14 - 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR = 1.63; 95% CI 1.07 - 2.46, p=0.02); there was significant heterogeneity (I2 = 80%, pheterogeneity<0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR=0.82, 95% CI 0.74 - 0.90, p<0.001 for OS) and in basal-like tumors (HR=0.64, 95% CI 0.52 - 0.80, p<0.001 for OS), pinteraction 0.005.

    CONCLUSION: The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like BC. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.

  • 5.
    Mauri, Davide
    et al.
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;PACMeR Athens, Evidence Based Dept, Athens, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Tsali, Lampriani
    PACMeR Athens, Evidence Based Dept, Athens, Greece.
    Polyzos, Nikolaos P.
    Hosp Univ Dexeus, Barcelona, Spain.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Zafeiria, Georgia
    Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Kalopita, Konstantina
    Alexandra Gen Hosp, Dept Anaesthesiol & Pain Med, Athens, Greece.
    Tsiara, Anna
    Univ Athens, Dept Med Oncol, Athens, Greece.
    Yerolatsite, Melina
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Zarkavelis, Georgios
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Kampletsas, Eleftherios
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Mouzaki, Ioanna
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Ntellas, Panagiotis
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Hills, Panagiotis
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Pentheroudakis, Georgios
    Univ Hosp Ioannina, Dept Med Oncol, S Niarchos Ave, TK-45500 Ioannina, Greece;Soc Study Clonal Heterogene Neoplasia EMEKEN, Ioannina, Greece.
    Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies2019In: Balkan Union of Oncology. Journal, ISSN 1107-0625, Vol. 24, no 4, p. 1314-1325Article in journal (Refereed)
    Abstract [en]

    Purpose: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. Methods: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. Results: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. Conclusions: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies.

  • 6.
    Mauri, Davide
    et al.
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Zafeiri, Georgia
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Yerolatsite, Melina
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Tsali, Lampriani
    Gen Hosp Arta, Dept Internal Med, Arta, Greece.
    Zarkavelis, Georgios
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Tsiare, Anna
    Alexandra Gen Hosp, Dept Med Oncol, Athens, Greece.
    Polyzos, Nikolaos P.
    Hosp Univ Dexeus, Barcelona, Spain.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Kalopita, Konastantina
    Alexandra Gen Hosp, Dept Anaesthesiol & Pain Med, Athens, Greece.
    Kampletsas, Eleftherios
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Papadaki, Alexandra
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece;EMEKEN, Ioannina, Greece.
    Peponi, Evangelia
    Univ Hosp Ioannina, Dept Radiotherapy, Ioannina, Greece.
    Kapoulitsa, Fani
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Filis, Panagiotis
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece.
    Pentheroudakis, Georgios
    Univ Hosp Ioannina, Dept Med Oncol, Ioannina 45500, Greece;EMEKEN, Ioannina, Greece.
    Global coverage and consistency of guideline recommendations for cancer cachexia on the Web in 2011 and 20182019In: Contemporary Oncology / Wspólczesna Onkologia, ISSN 1428-2526, Vol. 23, no 2, p. 100-109Article in journal (Refereed)
    Abstract [en]

    Introduction: Cancer cachexia is a common associate of cancer and has a negative impact on both patients' quality of life and overall survival. Nonetheless its management remains suboptimal in clinical practice. Provision of medical recommendations in websites is of extreme importance for medical decision making and translating evidence into clinical practice. Aim of the study: To scrutinize the magnitude, consistency and changes over time of cancer-cachexia recommendations for physicians on the Web among oncology related societies. Intercontinental, continental, national and socioeconomic variations were further analyzed. Material and methods: Web identification of oncology related societies and prospective analyses of relative Web guideline recommendations for physicians on cancer-cachexia at different time-points. Results: In June 2011, we scrutinized 144,000 Web pages. We identified 275 societies, of which 270 were eligible for analyses: 67 were international (African, American, Asian, European, Oceania and Intercontinental), 109 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology. Conclusions: The magnitude of cancer cachexia recommendations for physicians on the Web at a global level was scant both for coverage and consistency, and at any time-point considered: 3.7% (10/270) in 2011 and 8.1% (22/270) in 2018. The proportion of societies giving evidence-based and updated recommendations for cancer cachexia for physicians was only 1.1% (3/270) in 2011 and 2.96% (8/270) in 2018. Continent, national highest developmental index, oncology tradition and economic-geographic areas were not found to influence Web guideline provision.

  • 7.
    Mjelstad, AnneMarthe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zakariasson, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Valachis, Antonis
    Örebro Univ, Dept Oncol, Fac Med & Hlth, Örebro, Sweden; Mälarsjukhuset, Dept Oncol Sörmland, Eskilstuna, Sweden.
    Optimizing antiresorptive treatment in patients with bone metastases: time to initiation, switching strategies, and treatment duration2019In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 27, no 10, p. 3859-3867Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to investigate the optimal use of antiresorptive therapy in patients with metastatic cancer in terms of time to treatment initiation, switching strategy in case of skeletal-related event (SRE) or skeletal disease progression, and treatment efficacy beyond 2 years.

    Methods: We conducted a single-center retrospective cohort study including consecutive cancer patients with bone metastases that have received antiresorptive treatment between 2009 and 2015. The outcomes of interest were the time to first and subsequent symptomatic skeletal event (SSE), the skeletal morbidity rate, and the incidence of antiresorptive therapy-specific adverse events depending on the research question.

    Results: In total, 255 patients included in our study cohort. The time to treatment initiation (direct (n = 143 patients) vs. delayed (n = 87 patients) defined as > 3 months after diagnosis of bone metastases) was not found to influence the time to SSE in (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65–1.34) with comparable toxicity. Switching strategy after first SRE or due to skeletal disease progression from bisphosphonates to denosumab was independently associated with longer time to SRE (HR 0.47, 95% CI 0.25–0.88, p value = 0.019) compared with continuation with the same bisphosphonate. Using the landmark approach at 24 months and including 121 patients that survived for more than 2 years, we found that treatment continuation beyond 2 years was associated with longer time to first SSE after 2 years (HR 0.41; 95% CI 0.19–0.93).

    Conclusions: Our hypothesis-generating results support a more individualized approach on antiresorptive treatment including the lack of detrimental effect when the treatment is delayed, the potential benefit of switching strategy after skeletal disease progression or SSE, and the benefit of continuing antiresorptive treatment beyond 2 years.

     

  • 8.
    Mjelstad, AnneMarthe
    et al.
    Faculty of Medicine, Uppsala University, Uppsala, Sweden.
    Zakariasson, Gustav
    Faculty of Medicine, Uppsala University, Uppsala, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Oncology Sörmland, Mälarsjukhuset, Eskilstuna, Sweden.
    Optimizing antiresorptive treatment in patients with bone metastases: time to initiation, switching strategies, and treatment duration2019In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 27, no 10, p. 3859-3867Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to investigate the optimal use of antiresorptive therapy in patients with metastatic cancer in terms of time to treatment initiation, switching strategy in case of skeletal-related event (SRE) or skeletal disease progression, and treatment efficacy beyond 2 years.

    METHODS: We conducted a single-center retrospective cohort study including consecutive cancer patients with bone metastases that have received antiresorptive treatment between 2009 and 2015. The outcomes of interest were the time to first and subsequent symptomatic skeletal event (SSE), the skeletal morbidity rate, and the incidence of antiresorptive therapy-specific adverse events depending on the research question.

    RESULTS: In total, 255 patients included in our study cohort. The time to treatment initiation (direct (n = 143 patients) vs. delayed (n = 87 patients) defined as > 3 months after diagnosis of bone metastases) was not found to influence the time to SSE in (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65-1.34) with comparable toxicity. Switching strategy after first SRE or due to skeletal disease progression from bisphosphonates to denosumab was independently associated with longer time to SRE (HR 0.47, 95% CI 0.25-0.88, p value = 0.019) compared with continuation with the same bisphosphonate. Using the landmark approach at 24 months and including 121 patients that survived for more than 2 years, we found that treatment continuation beyond 2 years was associated with longer time to first SSE after 2 years (HR 0.41; 95% CI 0.19-0.93).

    CONCLUSIONS: Our hypothesis-generating results support a more individualized approach on antiresorptive treatment including the lack of detrimental effect when the treatment is delayed, the potential benefit of switching strategy after skeletal disease progression or SSE, and the benefit of continuing antiresorptive treatment beyond 2 years.

  • 9.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Malarsjukhuset, Dept Oncol, 34 Kungsvagen, SE-63188 Eskilstuna, Sweden..
    Kafantaris, Ioannis
    Malarsjukhuset, Dept Pulm Med, SE-63188 Eskilstuna, Sweden..
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Anesthesia Surg Serv & Intens Care, SE-17176 Stockholm, Sweden..
    Valachis, Antonios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Malarsjukhuset, Dept Oncol, 34 Kungsvagen, SE-63188 Eskilstuna, Sweden..
    Validation and optimization of a predictive model for radiation pneumonitis in patients with lung cancer2016In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 12, no 2, p. 1144-1148Article in journal (Refereed)
    Abstract [en]

    The aim of the current retrospective study was to validate a predictive model for radiation pneumonitis (STRIPE) in an independent dataset and to investigate whether the addition of other potential risk factors could strengthen the accuracy of the model. Consecutive patients with non-small cell lung carcinoma (NSCLC; n=71) treated with definitive concurrent chemotherapy and radiotherapy were retrospectively assessed for radiation pneumonitis (RP). The results identified that 16 (23%) patients developed grade >= 2 RP. Furthermore, STRIPE score (intermediate vs. low risk) was independently associated with the development of RP [odds ratio (OR), 3.72; 95% confidence interval (CI), 1.00-13.89], whereas current smoking status was found to be protective against RP (OR, 0.09; 95% CI, 0.01-0.78). Similar discriminatory power of the STRIPE score was observed as in the original study. The addition of smoking status strengthened the model's discriminatory ability to predict RP. Thus, the addition of smoking status as a risk factor may strengthen the accuracy of the model for predicting RP in patients with NSCLC.

  • 10.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Single-agent versus combination chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and performance status 2: A literature-based meta-analysis of randomized studies2014In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 84, no 3, p. 209-214Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to compare the efficacy and tolerability of first-line treatment with combination versus single agent chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) 2.

    METHODS: A systematic literature search was performed to identify randomized trials comparing combination versus single agent chemotherapy in patients with advanced NCSLC. Both trials dedicated to PS 2 patients and trials that performed a subset analysis according to PS were included in the meta-analysis. Standard meta-analytic procedures were used to analyze the study outcomes.

    RESULTS: Twelve trials were considered eligible and were further analyzed. The use of combination chemotherapy resulted in a statistically significant better overall survival compared to single agent chemotherapy (11 trials, 1114 patients; hazard ratio (HR), 0.79, 95% confidence interval (CI): 0.71-0.88). The survival benefit was pronounced when platinum-based combination was used (HR: 0.71, 95% CI: 0.61-0.81) while no survival benefit was observed in non-platinum based combinations (HR: 0.96, 95% CI: 0.80-1.15). Grade 3/4 anemia (OR: 3.12, 95% CI: 1.55-6.27), thrombocytopenia (OR: 12.81, 95% CI: 4.65-33.10), and neutropenia (OR: 7.91, 95% CI: 3.97-15.78) but not febrile neutropenia were significantly more frequent with combination chemotherapy.

    CONCLUSION: This meta-analysis provides evidence supporting the use of combination chemotherapy in patients with NSCLC and PS 2. However, the patients should be informed about the higher risk for toxicity with the combination chemotherapy and the final treatment strategy should be individualized.

  • 11.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Abu Sabaa, Amal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Flogegard, Max
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Does the omission of vincristine affect outcome and survival in patients with diffuse large B-cell lymphoma?2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 1006PDArticle in journal (Other academic)
  • 12.
    Mörth, Charlott
    et al.
    Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden; Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Abu Sabaa, Amal
    Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Marshall, Katharina
    Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Hedström, Gustaf
    Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Flogegård, Max
    Department of Internal Medicine, Falun General Hospital, Falun, Sweden.
    Baecklund, Eva
    Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Enblad, Gunilla
    Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Autoimmune disease in patients with diffuse large B-cell lymphoma: occurrence and impact on outcome2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 8, p. 1170-1177Article in journal (Refereed)
    Abstract [en]

    Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well as the impact of AID on outcome has not been extensively studied. The main purpose of this study was to establish the occurrence of AIDs in a population-based cohort of DLBCL patients and to compare outcomes in patients with or without AID treated with rituximab(R)-CHOP/CHOP-like treatment. We also aimed to analyse gender differences and the potential role of different AIDs on outcome and the frequency of treatment-associated neutropenic fever.

    Patients and methods: All adult patients treated 2000-2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n = 612). Lymphoma characteristics, outcome and the presence of AID were obtained through medical records.

    Results: The number of patients with AID was 106 (17.3%). Thyroid disease dominated (n = 33, 31.1%) followed by rheumatoid arthritis (RA) (n = 24, 22.6%). The proportion of AID was significantly higher in females (59/254, 23.2%) vs. in males (47/358, 13.1%) (p = .001). In the whole cohort there was no difference in event free survival (EFS) or overall survival (OS) between patients with or without AID. However, patients with an AID primarily mediated by B-cell responses (thyroid disorders excluded) had a worse OS (p = .037), which seemed to affect only women. The AID group more often had neutropenic fever after first treatment (16.0% vs 8.7%, p = .034) and those with neutropenic fever had a worse OS (p = .026) in Kaplan-Meier analyses.

    Conclusion: There is a high prevalence of AID among patients with DLBCL. AIDs categorized as primarily B-cell mediated (in this study mainly RA, systemic lupus erythematosus and Sjögren's syndrome) may be associated with inferior OS. AID patients may be more prone to neutropenic fever compared to patients without concomitant AID.

  • 13.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Mälarsjukhuset, Canc Ctr, Eskilstuna, Sweden.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sabaa, Amal Abu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Flogegård, Max
    Falun Gen Hosp, Dept Internal Med, Falun, Sweden.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Does the omission of vincristine in patients with diffuse large B cell lymphoma affect treatment outcome?2018In: Annals of Hematology, ISSN 0939-5555, E-ISSN 1432-0584, Vol. 97, no 11, p. 2129-2135Article in journal (Refereed)
    Abstract [en]

    The standard treatment for diffuse large B cell lymphoma (DLBCL) is rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine (VCR), and prednisone). Maintaining high dose intensity of cytotoxic treatment has been associated with better outcome but little is known about the role of maintaining VCR. This study aimed to answer whether the omission of vincristine due to neurotoxicity affects patient outcome. A Swedish cohort of patients primarily treated with curative intent for DLBCL or high-grade malignant B cell lymphoma was retrospectively analyzed. In total, 541 patients treated between 2000 and 2013 were included. Omission of VCR was decided in 95 (17.6%) patients and was more often decided during the last three cycles (n = 86, 90.5%). The omission of VCR did not affect disease-free or overall survival neither in the whole cohort nor in elderly patients. On the contrary, the relative dose intensity of doxorubicin was associated with overall survival (p = 0.014). Kidney or adrenal involvement (p = 0.014) as well as bulky disease (p = 0.037) was found to be associated with worse overall survival. According to our results, clinicians can safely decide to omit VCR in case of severe neurotoxicity due to VCR but should be aware of the importance of giving adequate doses of doxorubicin during treatment given the growing body of evidence on the role of dose intensity on survival. Considering the association of bulky disease and kidney/adrenal manifestation of lymphoma on survival, further studies should focus on whether the treatment options for these subgroups need to be individualized.

  • 14. Nearchou, Andreas Demetrios
    et al.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lind, Pehr
    Akre, Olof
    Sandstrom, Per
    Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine-kinase inhibitors (TKIs): A literature-based meta-analysis.2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 4SArticle in journal (Other academic)
  • 15.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Meta-analysis of randomized clinical evidence of chemotherapy, radiotherapy and endocrine therapy in breast cancer2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

     Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Despite the growing body of randomized controlled trials (RCTs) regarding the use of various treatment strategies (chemotherapy, endocrine therapy, radiotherapy) in breast cancer, the efficacy of some strategies remains unclear and questionable. A meta-analysis, by combining the results of all available trials that studied the same question, could help to reduce the level of uncertainty and provide reliable conclusions about the role of various therapeutic choices for breast cancer patients.Objective: The purpose of this thesis was to identify controversial therapeutic strategies in the treatment of breast cancer and to perform, when possible, meta-analyses to find out which of these strategies are valuable in breast cancer therapy. We conducted 7 separate meta-analyses in order to answer to 7 different clinical questions. We choose 7 topics with controversial results in the therapeutic strategy of breast cancer patients, namely the role of bisphosphonates as antitumor therapy and as preventive agents against fractures in adjuvant setting, the risk of osteonecrosis of the jaw (ONJ) with the use of bisphosphonates in adjuvant setting, the use of fulvestrant in advanced breast cancer, the safety of partial breast irradiation (PBI) compared with whole-breast radiotherapy (WBRT), the role of bevacizumab in advanced breast cancer and finally the value of trastuzumab as neoadjuvant therapy in Her2-positive breast cancer patients.Materials and Methods: In all 7 meta-analyses we used the same basic principles of meta-analysis, with some minor but necessary changes in order to fit our methodology to specific aims of each trial. In general, we conducted systematic reviews of all English and non-English medical literature using MEDLINE, the Cochrane Controlled Trials Register and ISI Web of Knowledge. We set no year restriction. The references of all eligible trials were also searched in order to find any potentially eligible trial that it was not identified by our searching algorithm. Abstracts of major meetings were also searched. Eligible studies were identified according to prespecified criteria for each meta-analysis. Data extraction was conducted independently by two investigators. In case of discrepancy, consensus was reached by involvement of a third investigator. When data on the outcome were not available from trials, we contacted the primary investigators of the eligible trials. Data synthesis was perfomed by choosing the appropriate effect size measure (Odds Ratio, Risk Ratio or Hazard Ratio) for each outcome and by combining the results using fixed- or random-effects models.Results: Regarding bisphosphonates in adjuvant setting, pooled results showed no statistical significant differences with the use of bisphosphonates in early breast cancer versus non-use for the overall number of deaths (summary OR, 0.708; 95% CI, 0.482–1.041; p-value =0.079), disease recurrences(summary OR, 0.843; 95% CI, 0.602–1.181; p-value =0.321), and bone metastases (summary OR, 0.925; 95% CI, 0.768–1.114; p-value =0.413). Subgroup analyses for disease recurrences according to the type of bisphosphonate used showed a statistically significant lower risk for disease recurrences with zoledronic acid (6 trials, OR, 0.675; 95% CI, 0.479–0.952; p-value = 0.025). In addition, bisphosphonates did not reduce fracture rate (OR=0.99, 95% CI=0.73–1.34) neither in postmenopausal women (OR=0.82, 95% CI=0.55–1.20) nor in women with breast cancer receiving aromatase inhibitors (OR=0.79, 95% CI=0.53–1.17). Overall, treatment with bisphosphonates was significantly associated with the occurrence of osteonecrosis of the jaw (ONJ) (OR = 3.23, 95% CI = 1.7–8) compared with no use but it was a rare event, occurring in 13 (0.24%) of the 5,312 patients receiving bisphosphonates.Considering fulvestrant, we found no difference between fulvestrant versus other hormonal agents regarding overall survival (HR: 1.047, 95% CI: 0.688–1.592; p-value = 0.830) and time to tumor progression (HR: 0.994, 95% CI: 0.691–1.431; p-value = 0.975).Partial breast irradiation (PBI) did not influence survival (OR 0.912, 95% CI, 0.674–1.234, p-value = 0.550) compared with WBRT but it was found to lead to statistically significant higher risk for developing local recurrences (pooled OR 2.150, 95% CI, 1.396–3.312; p-value = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p-value < 0.0001).The combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in progression-free survival compared with chemotherapy alone (HR = 0.70, 95% CI = 0.60–0.82, p-value = 9.3x10-6), especially when bevacizumab was combined with taxanes. However, the pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (pooled HR = 0.90, 95% CI 0.80–1.03, p-value = 0.119).Finally, the use of trastuzumab as neoadjuvant therapy lead to higher absolute pathologic complete response (pCR) rate (38% in trastuzumab arm in comparison with 21% in no trastuzumab arm) (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). Two out of 217 (0.9%) patients in the trastuzumab arms presented congestive heart failure compared with none in the chemotherapy alone arms.Conclusions: The meta-analysis of bisphosphonates in adjuvant breast cancer therapy showed that currently available randomized evidence does not support the hypothesis that using bisphosphonates in adjuvant treatment of early breast cancer alters the natural course of the disease. In addition bisphosphonates do not seem to prevent bone fractures. However, ONJ is a rare event in breast cancer patients treated with adjuvant use of bisphosphonates.Our meta-analysis of fulvestrant suggests that fulvestrant 250 mg is similar to other hormonal agents with respect to efficacy measures with equal or even better tolerability profile compared with other hormonal agents.Our meta-analysis of PBI, despite the fact that it is based on limited randomized evidence, suggests that PBI is a safe treatment modality as it does not seem to jeopardize survival compared with standard WBRT. Nevertheless, the issue of locoregional recurrence needs to be further addressed.The results of the meta-analysis of bevacizumab show that the addition of bevacizumab to chemotherapy offers a statistically significant improvement in progression free survival in patients with metastatic breast cancer but does not benefit overall survival. In addition, clinical significance of this improvement is questionable. As a result, bevacizumab treatment cannot be suggested for treatment of 1st line metastatic breast cancer,Finally, the meta-analysis of trastuzumab as neoadjuvant treatment underscores the beneficial effects of trastuzumab treatment in neoadjuvant regimens among HER2-positive breast cancer patients in terms of pCR. Of interest, no additional cardiotoxicity was documented in the trastuzumab arms.

  • 16.
    Valachis, Antonis
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Carlsson, L.
    Department of Oncology, Sundsvall County Hospital, Sundsvall, Sweden.
    Sundqvist, M.
    Breast Unit, Department of Surgery, Kalmar County Hospital, Kalmar, Sweden.
    Li, B.
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Chiesa, F.
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Uhde, M.
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Sanglier, T.
    PHC Data Science, F Hoffmann-La Roche Ltd, Basel, Switzerland.
    Use of subcutaneous and intravenous trastuzumab: Real-world experience from three hospitals in Sweden2019In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, no 4, article id P6-17-24Article in journal (Other academic)
  • 17.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Mamounas, Eleftherios P.
    Univ Florida, Hlth Canc Ctr Orlando Hlth, Comprehens Breast Program, Orlando, FL USA.
    Mittendorf, Elizabeth A.
    Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, Houston, TX 77030 USA.
    Hayashi, Naoki
    St Lukes Int Hosp, Dept Breast Surg, Tokyo, Japan.
    Ishitobi, Makoto
    Osaka Int Canc Inst, Dept Breast Surg, Osaka, Japan;Osaka Int Canc Inst, Dept Endocrine Surg, Osaka, Japan.
    Natoli, Clara
    Univ G DAnnunzio, Dept Oral Med & Biotechnol Sci, Chieti, Italy.
    Fitzal, Florian
    Med Univ Vienna, Dept Surg, Breast Hlth Ctr, Vienna, Austria.
    Rubio, Isabel T.
    Univ Hosp VAll dHebron, Breast Canc Ctr, Breast Surg Oncol, Barcelona, Spain.
    Tiezzi, Daniel G.
    Univ Sao Paulo, Ribeirao Preto Med Sch, Breast Dis Div, Dept Gynecol & Obstet, Sao Paulo, Brazil.
    Shin, Hee-Chul
    Chung Ang Univ Hosp, Dept Surg, Seoul, South Korea.
    Anderson, Stewart J.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Natl Surg Adjuvant Breast & Bowel Project,Biostat, Pittsburgh, PA 15261 USA.
    Hunt, Kelly K.
    Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, Houston, TX 77030 USA.
    Matsuda, Naoko
    St Lukes Int Hosp, Dept Breast Surg, Tokyo, Japan.
    Ohsumi, Shozo
    NHO Shikoku Canc Ctr, Dept Breast Oncol, Matsuyama, Ehime, Japan.
    Totomi, Athina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nilsson, Cecilia
    Vastmanlands Cty Hosp, Ctr Clin Res, Vasteras, Sweden.
    Risk factors for locoregional disease recurrence after breast‐conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta‐analysis2018In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 124, no 14, p. 2923-2930Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT. METHODS: Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively. RESULTS: A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN+disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively. CONCLUSIONS: BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up.

  • 18.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nearchou, Andreas
    Comments on 'High versus low radioiodine activity in patients with differentiated thyroid cancer: A meta-analysis' Reply2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 6, p. 1240-1241Article in journal (Refereed)
  • 19.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nearchou, Andreas
    High versus low radioiodine activity in patients with differentiated thyroid cancer: A meta-analysis2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 6, p. 1055-1061Article, review/survey (Refereed)
    Abstract [en]

    Background. The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design. A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85-1.04, p-value = 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72-1.06, p-value = 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93-1.07, p-value = 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion. Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity.

  • 20.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nearchou, Andreas D.
    Lind, Pehr
    Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis2014In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 144, no 3, p. 443-455Article, review/survey (Refereed)
    Abstract [en]

    This meta-analysis investigates the oncological safety of breast-conserving therapy BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral breast recurrence (IBR) or CBC and grades these factors based on the level of evidence. A PubMed search was conducted through April 2013 to identify studies that described the risk for IBR and CBC after BCT in BRCA-mutation carriers versus non-carriers as well as studies that investigated risk factors for IBR and CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when sufficient studies were available. Ten studies investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR 1.45, 95 % CI 0.98-2.14). However, a significant higher risk for IBR in BRCA-mutation carriers was observed in studies with a median follow-up a parts per thousand yen7 years (RR 1.51, 95 % CI 1.15-1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95 % CI 2.50-5.08). Use of adjuvant chemotherapy and oophorectomy were associated with a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use of tamoxifen, and age at first breast cancer. Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk for IBR. However, several aspects should be taken into account before the final decision-making.

  • 21.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nearchou, Andreas
    Lind, Pehr
    Mauri, Davide
    Lapatinib, trastuzumab or the combination added to preoperative chemotherapy for breast cancer: a meta-analysis of randomized evidence2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 135, no 3, p. 655-662Article, review/survey (Refereed)
    Abstract [en]

    We compared the efficacy and safety of the addition of lapatinib versus trastuzumab or their combination to neoadjuvant chemotherapy in HER2-positive breast cancer. 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, and toxicity. Pooled risk ratios (RR) were estimated for each endpoint with fixed or random effects models, depending on between studies heterogeneity. Six trials were identified with 1,494 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm versus lapatinib plus chemotherapy (RR 1.25, 95 % confidence interval [CI] 1.08-1.43; p = 0.003) (6 trials; 1,494 patients). Probability to pCR was significantly higher in the group receiving lapatinib and trastuzumab than in the group with trastuzumab alone (RR 1.39, 95 % CI 1.20-1.63; p < 0.001) (4 trials; 779 patients). Grade III-IV diarrhea and dermatologic toxicities were statistically more frequent in patients receiving lapatinib. No differences were observed regarding cardiac adverse events among patients receiving trastuzumab, lapatinib, or their combination. These data supports the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer in the neoadjuvant setting. The direct comparison of trastuzumab and lapatinib showed that lapatinib is inferior in terms of pCR and associated with a higher risk for toxicity.

  • 22.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nearchou, Andreas
    Polyzos, Nikolaos P.
    Lind, Pehr
    Cardiac toxicity in breast cancer patients treated with dual HER2 blockade2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 9, p. 2245-2252Article in journal (Refereed)
    Abstract [en]

    Although dual HER2 blockade shows promising results in patients with HER2-positive breast cancer it is unclear whether this treatment strategy increases the risk for cardiac adverse events. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. We searched Medline, the Cochrane library, as well as the electronic abstract databases of the major international congresses' proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) therapy in breast cancer. The trials were considered eligible if the only systematic difference between the study arms was the type of anti-HER2 therapy used. Study outcomes were the congestive heart failure (CHF) grade 3 and left ventricular ejection fraction (LVEF) decline <50% or more than 10% from baseline. Six trials were considered eligible. Overall incidence results for CHF in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 0.88% (95% CI: 0.47-1.64%) and 1.49% (95% CI: 0.98-2.23%). The incidence of LVEF decline was 3.1% (95% CI: 2.2-4.4%) and 2.9% (95% CI: 2.1-4.1%), respectively. The OR of CHF between anti-HER2 combination and monotherapy was 0.58 (95% CI: 0.26-1.27, p-value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53-1.48, p-value= 0.64). This meta-analysis provides evidence supporting comparable cardiac toxicity between anti-HER2 combination therapy and anti-HER2 monotherapy. What's new? Breast cancers caused by HER2 overexpression generally have poor prognosis. Drugs targeting the HER2 receptor can thwart the cancer, but also increase the risk of heart problems. New treatments are coming along which combine two anti-HER2 agents for an even greater anticancer effect, but will these dual therapies cause worse cardiac effects? In this report, the authors collected data from trials comparing dual anti-HER2 therapy with anti-HER2 monotherapy, and specifically looked at risk of cardiac side effects. They conclude that doubling up on anti-HER2 drugs did not increase the cardiac toxicity compared with the use of anti-HER2 drugs individually.

  • 23.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanlands Cty Hosp, Ctr Clin Res, Vasteras, Sweden..
    Cardiac risk in the treatment of breast cancer: assessment and management2015In: Breast Cancer: Targets and Therapy, ISSN 1179-1314, E-ISSN 1179-1314, Vol. 7, p. 21-35Article, review/survey (Refereed)
    Abstract [en]

    As the number of long-term breast cancer survivors has increased, the side effects of adjuvant cancer therapy, such as cardiac toxicity, remain clinically important. Although the cardiac toxicity due to anthracyclines, radiotherapy, or trastuzumab is well-documented, several issues need to be clarified and are the subjects of extensive ongoing clinical research. This review summarizes the incidence of cardiac toxicity due to breast cancer adjuvant therapy and highlights the current trends in early detection and management of cardiac toxicities.

  • 24.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Polyzos, Nikolaos P.
    Role of Zoledronate in Aromatase Activity Should Be Considered in Future Studies In Reply2013In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 18, no 8, p. E26-E27Article in journal (Refereed)
  • 25.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Polyzos, Nikolaos P.
    Coleman, Robert E.
    Gnant, Michael
    Eidtmann, Holger
    Brufsky, Adam M.
    Aft, Rebecca
    Tevaarwerk, Amye J.
    Swenson, Karen
    Lind, Pehr
    Mauri, Davide
    Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer: A Systematic Review and Meta-Analysis2013In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 18, no 4, p. 353-361Article, review/survey (Refereed)
    Abstract [en]

    Background. The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer. Materials and Methods. We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70-1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio[OR], 0.94; 95% CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%. Conclusion. Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment. 

  • 26.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Malarsjukhuset, Dept Oncol, Eskilstuna, Sweden.
    Samonis, George
    Univ Hosp Heraklion, Infect Dis Unit, Dept Internal Med, Iraklion, Greece..
    Kofteridis, Diamantis P.
    Univ Hosp Heraklion, Infect Dis Unit, Dept Internal Med, Iraklion, Greece..
    The Role of Aerolized Colistin in the Treatment of Hospital-Acquired Pneumonia: Experience of Multicenter From Turkey Reply2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 5, p. E304-E305Article in journal (Other academic)
  • 27.
    Valachis, Antonis
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Sundqvist, Marie
    Breast Unit, Department of Surgery, Kalmar County Hospital, Kalmar, Sweden.
    Carlsson, Lena
    Department of Oncology, Sundsvall County Hospital, Sundsvall, Sweden.
    Li, Bing
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Chiesa, Flaminia
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Uhde, Milica
    Real World & Analytic Solutions (RWAS), IQVIA, Stockholm, Sweden.
    Sanglier, Thibaut
    PHC Data Science, F Hoffmann-La Roche Ltd, Basel, Switzerland.
    Use of subcutaneous and intravenous trastuzumab: real-world experience from three hospitals in Sweden2019In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 15, no 23, p. 2733-2741Article in journal (Refereed)
    Abstract [en]

    Aim: We aimed to describe the use of subcutaneous (sc.) trastuzumab use in a real-world setting.

    Patients & methods: This retrospective cohort study evaluated electronic medical records of patients with early breast cancer and trastuzumab use from January 2010 to February 2018 in three hospitals in Sweden.

    Results: In total, 363 patients received trastuzumab during study period. Of these, 217 (59.8%) patients started treatment with sc. trastuzumab and 146 (40.2%) with intravenous trastuzumab. After sc. trastuzumab approval, use of sc. trastuzumab increased from 70.2% in 2014 to 100% in 2017. Since 2013, 34 of 35 (97.4%) patients who started with intravenous trastuzumab switched to sc. formulation.

    Conclusion: Trastuzumab sc. quickly became the prevailing formulation for treatment in HER2-positive early breast cancer.

  • 28.
    Valachis, Antonis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Discrepancy in BRAF status among patients with metastatic malignant melanoma: A meta-analysis2017In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 81, p. 106-115Article, review/survey (Refereed)
    Abstract [en]

    The incidence of malignant melanoma is growing rapidly. Approximately half of the cases are BRAF mutated, making treatment with kinase inhibitors a (MEK and BRAF inhibitors) preferred choice in the advanced setting. The vast majority of these patients will benefit from the treatment. It is therefore of vital importance that the BRAF analysis is reliable and reflects the true nature of the tumour. Intraindividual tumour BRAF heterogeneity may exist, and changes of BRAF status over time might occur. We reviewed the literature by searching the PubMed database and 630 potentially relevant studies were identified. Thereafter, studies that investigated intralesional heterogeneity only, studies with <= 10 patients and studies that did not include adequate data to calculate discrepancy rates were excluded. Twenty-two studies met our inclusion criteria and were included in the meta-analysis. The pooled discrepancy rate between primary and metastatic lesions was 13.4% (95% confidence interval [CI]: 9.2-18.2%) while it was 7.3% (95% CI: 3.3-12.6) between two metastatic lesions. The number of patients whose tumoural BRAF status was changed from mutation to wild type and from wild type to mutation, respectively, was comparable. We conclude that a clinically meaningful discrepancy rate in BRAF status both between primary-metastatic and metastatic-metastatic melanoma lesions exists. Our results support the polyclonal model of melanomas in which subclones with different BRAF status co-exist in the same melanoma lesion. In addition, the results indicate a need for biopsy of a metastatic lesion for subsequent BRAF analysis when treatment with kinase inhibitors is considered.

  • 29.
    Zavos, A.
    et al.
    Senol Hellen Soc, Athens, Greece..
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Malarsjukhuset, Dept Oncol, S-63188 Eskilstuna, Sweden..
    Risk of chemotherapy-induced amenorrhea in patients with breast cancer: a systematic review and meta-analysis2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 6, p. 664-670Article, review/survey (Refereed)
    Abstract [en]

    Background: The aim of the study was to calculate the rate of chemotherapy-induced amenorrhea (CIA) after treatment with different adjuvant therapies in patients with breast cancer and to evaluate the risk factors for CIA based on the quality of evidence.Patient and methods: A search of PubMed and ISI Web of Science was performed. All published trials with female breast cancer patients who received adjuvant chemotherapy and presented data on the rate of CIA were considered eligible. The pooled rates of CIA were calculated by random effects model. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each potential risk factor for CIA by using the generic inverse weighted method.Results: We identified 580 potentially relevant studies, of which 75 were included in the analysis. Among 75 eligible studies, 19 different definitions of CIA have been used. The pooled rate of CIA was 55% (95% CI 50-60%) including 23 673 patients from 74 studies. The rate of CIA was increased by age with an estimate of 26% (95% CI 12-43%), 39% (95% CI 31-58%), and 77% (95% CI 71-83%) for women<35, 35-40, and>40 years old, respectively. Two risk factors were associated with the occurrence of CIA and were supported by strong level of evidence: older age (>40 years old), and the use of tamoxifen.Conclusions: This meta-analysis summarized the updated evidence on the impact of different adjuvant treatment regimens for breast cancer in menstruation and could serve as a helpful guide for oncologists during the discussion with their patients on fertility issues before decision on adjuvant therapy is made. A uniform definition of CIA is essential in future studies to make the interpretation of results more reliable.

  • 30.
    Zewenghiel, Luwam
    et al.
    Orebro Univ, Inst Med Sci, Campus USO, S-70182 Orebro, Sweden.
    Lindman, Henrik
    Akad Univ Hosp, Dept Oncol, Uppsala, Sweden.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Malarsjukhuset, Dept Oncol, Eskilstuna, Sweden.
    Impact of body mass index on the efficacy of endocrine therapy in patients with metastatic breast cancer - A retrospective two-center cohort study2018In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 40, p. 136-140Article in journal (Refereed)
    Abstract [en]

    Bakground: The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant. Methods: A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI. Results: In total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and Als and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively. Conclusions: No difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI.

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