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  • 1.
    Bergman, Marie
    et al.
    Department of Oncology, Hospital of Karlstad, Karlstad, Sweden.
    Fountoukidis, Georgios
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Smith, Daniel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ahlgren, Johan
    Regional Cancer Centre, Mid-Sweden Health Care Region, Uppsala, Sweden.
    Lambe, Mats
    Regional Cancer Centre, Mid-Sweden Health Care Region, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Effect of Smoking on Treatment Efficacy and Toxicity in Patients with Cancer: A Systematic Review and Meta-Analysis2022In: Cancers, ISSN 2072-6694, Vol. 14, no 17, article id 4117Article, review/survey (Refereed)
    Abstract [en]

    AIM: The aim of the present systematic review and meta-analysis was to summarize the current evidence on the potential impact of smoking during cancer treatment on treatment efficacy and toxicity irrespective of cancer type.

    METHODS: A systematic literature search was performed using two electronic databases for potentially eligible studies. Only studies based on multivariable analysis for the association between smoking, compared to non-smokers (never or former), and treatment efficacy or toxicity were included. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and corresponding 95% Confidence Intervals (CIs) were estimated through random-effects meta-analyses.

    RESULTS: In total, 97 eligible studies were identified, of which 79 were eligible for the pooled analyses. Smoking during radiation therapy, with or without chemotherapy, was associated with an increased risk of locoregional recurrence (pooled HR: 1.56; 95% CI: 1.28-1.91 for radiation therapy; pooled HR: 4.28; 95% CI: 2.06-8.90 for chemoradiotherapy) and worse disease-free survival (pooled HR: 1.88; 95% CI: 1.21-2.90 for radiation therapy; pooled HR: 1.92; 95% CI: 1.41-2.62 for chemoradiotherapy) as well as a higher risk for radiation-induced toxicity (pooled OR: 1.84; 95% CI: 1.32-2.56 for radiation therapy; pooled OR: 2.43; 95% CI: 1.43-4.07 for chemoradiotherapy) with low-to-moderate certainty of evidence. Smoking during treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with lung cancer was associated with worse progression-free survival compared to non-smokers (pooled HR: 1.43; 95% CI: 1.14-1.80; moderate certainty of evidence), whereas smoking was associated with improved progression-free survival in patients treated with checkpoint inhibitors (HR: 0.70; 95% CI: 0.58-0.84; moderate certainty of evidence). No statistically significant associations were observed between smoking and treatment efficacy or toxicity to chemotherapy.

    CONCLUSION: The present meta-analysis confirms earlier evidence of the negative impact of smoking during radiation therapy, with or without chemotherapy, on treatment efficacy and radiation-induced toxicity as well as a negative impact of smoking on the efficacy of EGFR-TKIs and a positive impact on the efficacy of checkpoint inhibitors. The evidence is too weak to draw firm conclusions on the potential association between smoking and chemotherapy, whereas there is no evidence for pooled analyses regarding other types of systemic oncological therapy.

  • 2.
    Boman, Caroline
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Solna, Sweden.
    Zerdes, Ioannis
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Solna, Sweden.
    Mårtensson, Kira
    Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Stockholm, Sweden.
    Bergh, Jonas
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Solna, Sweden.
    Foukakis, Theodoros
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Solna, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Matikas, Alexios
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Solna, Sweden.
    Discordance of PD-L1 status between primary and metastatic breast cancer: A systematic review and meta-analysis2021In: Cancer Treatment Reviews, ISSN 0305-7372, E-ISSN 1532-1967, Vol. 99, article id 102257Article, review/survey (Refereed)
    Abstract [en]

    INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.

    METHODS: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.

    RESULTS: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).

    CONCLUSION: The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.

  • 3.
    Castelo-Branco, L.
    et al.
    Scientific and Medical Division, European Society for Medical Oncology (ESMO), Lugano, Switzerland.
    Pellat, A.
    Department of Gastroenterology and Digestive Oncology, Hôpital Cochin AP-HP, Université Paris Cité, Paris; Centre d'Épidémiologie Clinique, Hôtel Dieu, Paris, France.
    Martins-Branco, D.
    Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Academic Trials Promoting Team (ATPT), Brussels, Belgium.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Derksen, J. W. G.
    Julius Center for Health Sciences and Primary Care, Department of Epidemiology and Health Economics, University Medical Centre Utrecht, Utrecht University, Utrecht.
    Suijkerbuijk, K. P. M.
    Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
    Dafni, U.
    Laboratory of Biostatistics, Department of Nursing, National and Kapodistrian University of Athens, Athens; Frontier Science Foundation Hellas, Athens, Greece.
    Dellaporta, T.
    Frontier Science Foundation Hellas, Athens, Greece.
    Vogel, A.
    Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany; Toronto Center of Liver Disease, Toronto General Hospital, University Health Network, Toronto; Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
    Prelaj, A.
    AI-ON-Lab, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan; NEARLab, Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
    Groenwold, R. H. H.
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
    Martins, H.
    Business Research Unit, Iscte Business School, ISCTE-IUL, Lisbon, Portugal.
    Stahel, R.
    ETOP IBCSG Partners Foundation, Berne, Switzerland.
    Bliss, J.
    ICR-CTSU, Division of Clinical Studies, The Institute of Cancer Research, London, UK.
    Kather, J.
    Else Kroener Fresenius Center for Digital Health, Technical University Dresden, Dresden; Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
    Ribelles, N.
    Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain.
    Perrone, F.
    Clinical Trial Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
    Hall, P. S.
    Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
    Dienstmann, R.
    Oncoclinicas Precision Medicine, Oncoclinicas Group, São Paulo, Brazil; Oncology Data Science Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
    Booth, C. M.
    Department of Oncology, Queen's University, Kingston; Department of Public Health Sciences, Queen's University, Kingston, Canada.
    Pentheroudakis, G.
    Scientific and Medical Division, European Society for Medical Oncology (ESMO), Lugano, Switzerland.
    Delaloge, S.
    Department of Cancer Medicine, Gustave Roussy, Villejuif, France.
    Koopman, M.
    Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
    ESMO Guidance for Reporting Oncology real-World evidence (GROW)2023In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 34, no 12, p. 1097-1112Article in journal (Refereed)
  • 4.
    Colleoni, Marco
    et al.
    International Breast Cancer Study Group, Milan, Italy; Division of Medical Senology, Milan, Italy.
    Luo, Weixiu
    International Breast Cancer Study Group Statistical Center, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA.
    Karlsson, Per
    International Breast Cancer Study Group and Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Chirgwin, Jacquie
    International Breast Cancer Study Group, Australia and New Zealand Breast Cancer Trials Group, and Box Hill and Maroondah Hospitals, Monash University, Melbourne, VIC, Australia.
    Aebi, Stefan
    International Breast Cancer Study Group and Lucerne Canton Hospital, Lucerne, Switzerland.
    Jerusalem, Guy
    International Breast Cancer Study Group, Centre Hospitalier Universitaire de Liège, Liège University, Liège, Belgium.
    Neven, Patrick
    International Breast Cancer Study Group and Multidisciplinary Breast Center, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium.
    Hitre, Erika
    International Breast Cancer Study Group and National Institute of Oncology, Budapest, Hungary.
    Graas, Marie-Pascale
    International Breast Cancer Study Group and Centre Hospitalier Chrétien Clinique St Joseph, Liège, Belgium.
    Simoncini, Edda
    International Breast Cancer Study Group and ASST Spedali Civili di Brescia, Brescia, Italy.
    Kamby, Claus
    Danish Breast Cancer Group and Rigshospitalet, Copenhagen, Denmark.
    Thompson, Alastair
    Scottish Cancer Trials Breast Group and The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    Loibl, Sibylle
    German Breast Group, Neu-Isenburg, Germany.
    Gavilá, Joaquín
    SOLTI Group and Fundación Instituto Valenciano de Oncologia, Valencia, Spain.
    Kuroi, Katsumasa
    Japan Breast Cancer Research Group and Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
    Marth, Christian
    Austrian Breast & Colorectal Cancer Study Group and Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria.
    Müller, Bettina
    Chilean Cooperative Group for Oncologic Research, Providencia, Santiago, Chile.
    O'Reilly, Seamus
    Cancer Trials Ireland and Cork University Hospital, Cork, Ireland.
    Di Lauro, Vincenzo
    International Breast Cancer Study Group and Centro di Riferimento Oncologico di Aviano, Aviano, Italy.
    Gombos, Andrea
    Medical Oncology Clinic, Institute Jules Bordet, Brussels, Belgium.
    Ruhstaller, Thomas
    Swiss Group for Clinical Cancer Research, International Breast Cancer Study Group, and Breast Center St Gallen, St Gallen, Switzerland.
    Burstein, Harold
    Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
    Ribi, Karin
    International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
    Bernhard, Jürg
    International Breast Cancer Study Group Coordinating Center, Bern, Switzerland; Bern University Hospital, Inselspital, Bern, Switzerland.
    Viale, Giuseppe
    European Institute of Oncology, Milan, Italy; International Breast Cancer Study Group Central Pathology Office and University of Milan, Milan, Italy.
    Maibach, Rudolf
    International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
    Rabaglio-Poretti, Manuela
    International Breast Cancer Study Group, Inselspital, Bern, Switzerland; Bern University Hospital, Inselspital, Bern, Switzerland.
    Gelber, Richard D.
    International Breast Cancer Study Group Statistical Center, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard T H Chan School of Public Health, Boston, MA, USA; Frontier Science & Technology Research Foundation, Boston, MA, USA.
    Coates, Alan S.
    International Breast Cancer Study Group, Milan, Italy; Harvard Medical School, Boston, MA, USA.
    Di Leo, Angelo
    International Breast Cancer Study Group, Milan, Italy; Harvard T H Chan School of Public Health, Boston, MA, USA .
    Regan, Meredith M.
    International Breast Cancer Study Group Statistical Center, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
    Goldhirsch, Aron
    International Breast Cancer Study Group, Milan, Italy; European Institute of Oncology, Milan, Italy.
    The SOLE Investigators,
    Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial2018In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 19, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.

    METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.

    FINDINGS: Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).

    INTERPRETATION: In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.

    FUNDING: Novartis and the International Breast Cancer Study Group.

  • 5.
    Derksen, J. W. G.
    et al.
    Dept. Julius Center for Health Sciences and Primary Care, UMC-University Medical Center Utrecht, Utrecht, Netherlands.
    Branco, D. Martins
    Clinical Trials Support Unit, Institute Jules Bordet, Brussels, Belgium.
    Pellat, A.
    Medical Oncology, Hopital Saint-Antoine, Paris, France.
    Van Nassau, S. C. M. W.
    Medical Oncology, UMC - University Medical Center Utrecht, Utrecht, Netherlands.
    Valachis, A.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Dept. of Oncology.
    Aggarwal, A.
    Institute of Cancer Policy, KCL - King's College London, London, UK.
    Koopman, M.
    Medical Oncology, UMC - University Medical Center Utrecht, Utrecht, Netherlands.
    Pentheroudakis, G.
    Scientific and Medical Division, ESMO - European Society for Medical Oncology, Lugano, Switzerland.
    Castelo-Branco, L.
    Scientific and Medical Division, ESMO - European Society for Medical Oncology, Lugano, Switzerland.
    Delaloge, S.
    Breast Oncology Department, Institut Gustave Roussy, Villejuif, France.
    Real-world evidence contributions to European medicines agency's safety and efficacy evaluations of oncology targeted therapies between 2018-20222023In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 34, no Suppl. 2, p. S930-S930, article id 1702PArticle in journal (Other academic)
    Abstract [en]

    Background: While Real-world Evidence (RWE) has documented value for safety monitoring and disease epidemiology, its objective contribution to safety and efficacy evaluations for regulatory purposes is still unclear. Here, we aim to describe the prevalence and type of RWE considered by European Medicines Agency (EMA) as contribution to efficacy and safety-related evidence generation among approved oncology targeted therapies...

    Methods: On March 10, 2023, we screened the medicines listing of EMA to identify all anti-cancer targeted therapies for solid malignancies with a decision date (initial marketing authorizations and extension of indications) between 2018-2022. We screened the European public assessment reports (EPARs) using a standardized approach to collect data on RWE. When generated pre-authorization, the RWE contribution to the final regulatory decision was classified as definitive, supportive, or non-supportive. For...

    Results: Out of a total of 1976 medicines, we identified 55 oncology targeted therapies, corresponding to 75 EPARs (indications), which are described in the table. The use of RWE in regulatory deliberations occurred in 24/75 (32%) EPARs, increasing from 30% in 2018-2020, to 34% in 2021-2022. Pre-authorization RWE was described in 20/24 (83%) EPARs, among which none were definitive, 8 RWE studies (in 7 EPARs) non-supportive, and 20 RWE studies (in 15 EPARs) were supportive of the decision. Published RWE...

    Conclusions: Over the past 5 years, RWE involvement in the approval of oncology targeted therapies in Europe tends to increase, with the majority being supportive for EMA regulatory decision making complementary to traditional clinical trials...

  • 6.
    Digkas, Evangelos
    et al.
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Smith, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Epidemiology and Biostatistics.
    Wennstig, Anna-Karin
    Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden; Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden.
    Matikas, Alexios
    Department of Oncology/Pathology, Karolinska Institute, Stockholm, Sweden; Breast Center, Karolinska Comprehensive Cancer Center and Karolinska University Hospital, Stockholm, Sweden.
    Tegnelius, Eva
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Incidence and risk factors of hypothyroidism after treatment for early breast cancer: a population-based cohort study2024In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 204, p. 79-87Article in journal (Refereed)
    Abstract [en]

    PURPOSE: An increased incidence of hypothyroidism among breast cancer survivors has been observed in earlier studies. The impact of the postoperative treatment modalities and their potential interplay on hypothyroidism development needs to be studied.

    METHODS: We conducted a population- and registry-based study using the Breast Cancer Data Base Sweden (BCBaSe) including females diagnosed with breast cancer between 2006 and 2012. In total, 21,268 female patients diagnosed with early breast cancer between 2006 and 2012, with no previous prescription of thyroid hormones and no malignant diagnosis during the last ten years before breast cancer diagnosis, were included in the final analysis.

    RESULTS: During the follow-up (median follow-up time 7.9 years), 1212 patients (5.7%) developed hypothyroidism at a median time of 3.45 years from the index date. No association of the systemic oncological treatment in terms of either chemotherapy or endocrine therapy and hypothyroidism development could be identified. A higher risk (HR 1.68;95% CI 1.42-1.99) of hypothyroidism identified among patients treated with radiation treatment of the regional lymph nodes whereas no increased risk in patients treated only with radiation therapy to the breast/chest wall was found (HR 1.01; 95% CI 0.86-1.19). The risk of hypothyroidism in the cohort treated with radiotherapy of the regional lymph nodes was present irrespective of the use of adjuvant chemotherapy treatment.

    CONCLUSIONS: Based on the results of our study, the implementation of hypothyroidism surveillance among the breast cancer survivors treated with radiotherapy of the regional lymph nodes can be considered as reasonable in the follow-up program.

  • 7.
    Digkas, Evangelos
    et al.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Tabiim, Anthony Jagri
    Department of Surgery, Korle-Bu Teaching Hospital, Accra, Ghana.
    Smith, Daniel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis2022In: Targeted oncology, ISSN 1776-2596, E-ISSN 1776-260X, Vol. 17, no 5, p. 507-515Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown.

    OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma.

    PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared.

    RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed.

    CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.

  • 8.
    Isheden, G.
    et al.
    Intelligent Decision Analytics AB, Solna, Sweden.
    Dalén, J.
    ICON Plc, Stockholm, Sweden.
    Holm, B.
    Novartis Sverige AB, Stockholm, Sweden.
    Lindman, H.
    Uppsala University Hospital, Uppsala, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Vertuani, S.
    Novartis Sverige AB, Stockholm, Sweden.
    SWEDISH NATIONWIDE REGISTER DATA AS A LOW-COST RESOURCE TO DETECT DRUG-REPURPOSING SIGNALS: A STUDY ON DE NOVO METASTATIC BREAST CANCER PATIENTS2022In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 25, no 12 Suppl., p. S375-S375, article id MSR128Article in journal (Other academic)
    Abstract [en]

    Objectives: Electronic health records have recently been highlighted as a low-cost resource to accelerate cancer therapeutics by drug repurposing discovery (Wu et al., JCO Clinical Cancer Informatics 2019:3, 1-9). The aim of this study was to test this approach on Swedish nationwide register data focusing on breast cancer cases with distant metastasis at initial diagnosis (de novo mBC). To demonstrate the feasibility of this methodology we i) evaluated the nine drug candidates identified by Wu et al. on our dataset, ii) generated drug repurposing hypotheses based on prescription drugs given to patients during metastatic breast cancer diagnosis/treatment.

    Methods: Patients diagnosed with de novo mBC between 2010 and 2020 were identified in the Swedish Cancer Register. Data on prescription drug use was collected from the National Prescribed Drug Register and survival data was collected from the National Cause of Death Register. Based on a 6-month window from diagnosis, drug repurposing candidates were evaluated using Cox proportional hazards models.

    Results: A total of 2,106 de novo mBC patients were included. The nine drug candidates found by Wu et al. (Rosuvastatin, Simvastatin, Amlodipine, Tamsulosin, Metformin, Omeprazole, Warfarin, Lisinoprol and Metroprolol) were not found significant in our data. However, a total of seven other drug repurposing hy-potheses were generated, with a plausible biological rationale for at least five of them (Calcium + Vitamin D, Morphine, Furosemide, Salbutamol and Ipratropium bromide, and Fentanyl). The other two were vaginal gel and Fluoride mouthwash.

    Conclusions: This study shows that the Swedish National Health Data Registers may be leveraged as a low-cost data source to detect drug repurposing signals. While results need to be interpreted with caution to not confuse causal relationships, the hypotheses generated in our study show a model for discovering noncancer drug effects on overall survival.

  • 9.
    Jonsson, Gabriel
    et al.
    Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden.
    Philipson, Louise
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Villman, Kenneth
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Upfront Radiotherapy in Patients With Asymptomatic Incurable Rectal Cancer: A Retrospective Cohort Study2020In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 40, no 10, p. 5853-5860Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIM: The optimal treatment sequencing for asymptomatic de novo metastatic rectal cancer is unclear. The aim of this study was to investigate the role of upfront radiotherapy, with or without chemotherapy on risk for local complications, in patients with asymptomatic advanced metastatic rectal cancer treated with palliative intention.

    PATIENTS AND METHODS: All patients with de novo metastatic rectal cancer diagnosed between January 2008 and December 2017 in two healthcare regions in Sweden (Örebro län, Sörmland) were identified and data were extracted from electronic medical records. Patients were divided into 3 groups based on treatment sequence: upfront radiotherapy, upfront chemotherapy, and only palliative surgery.

    RESULTS: In total, 102 patients were included in the study cohort, 30 patients in upfront radiotherapy group, 54 in upfront chemotherapy, and 18 in only palliative surgery group. Patients with only upfront CT [odds ratio (OR)= 5.10; 95% confidence interval (CI)=1.24-20.91, p=0.024] had a higher risk to suffer from a local complication compared to those who received upfront radiotherapy. Cause-specific Cox regression analysis among patients who received oncological therapy revealed that female patients [cause-specific hazard ratio (csHR)=3.61; 95% confidence interval (CI)=1.67-7.81] and upfront chemotherapy [csHR=1.85; 95% CI=1.11-3.77] were associated with increased cumulative incidence of local complication over time, whereas primary surgery with ostomy or stent with lower risk [csHR=0.45; 95% CI=0.21-0.99].

    CONCLUSION: Patients who received upfront radiotherapy, with or without chemotherapy, had fewer local complications due to primary tumor compared to patients who only received chemotherapy. This could indicate that radiotherapy to the primary tumor could be discussed with the patients as a first treatment option for asymptomatic metastatic rectal cancer to prevent local complications later during the disease.

  • 10.
    Joona, Therse Björkin
    et al.
    Department of Oncology, Västerås Central Hospital, Västerås, Sweden.
    Digkas, Evangelos
    Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden.
    Wennstig, Anna-Karin
    Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden.
    Nyström, Karin
    Örebro University, School of Medical Sciences. Department of Oncology.
    Nearchou, Andreas
    Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden.
    Nilsson, Cecilia
    Department of Oncology, Västerås Central Hospital, Västerås, Sweden.
    Pauksens, Karlis
    Department of Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Influenza vaccination in breast cancer patients during subcutaneous trastuzumab in adjuvant setting2020In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 184, no 1, p. 45-52Article in journal (Refereed)
    Abstract [en]

    Background: Despite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting.

    Methods: A prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured.

    Results: Twenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%,pvalue = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination.

    Conclusion: Breast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.

  • 11.
    Kamposioras, Konstantinos
    et al.
    Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
    Mauri, Davide
    Department of Medical Oncology, University Hospital of Ioannina, Ioannina, Greece.
    Papadimitriou, Konstantinos
    Early Clinical Trials Unit, Antwerp University Hospital, Antwerp, Belgium.
    Anthoney, Alan
    Leeds Institute of Medical Research at St James' Hospital, University of Leeds, Leeds, United Kingdom.
    Hindi, Nadia
    Department of Medical Oncology, University Hospital Virgen del Rocío, Sevilla, Spain; TERABIS Group, IBiS (Instituto de Biomedicina de Sevilla)/HUVR/CSIC/Universidad deSevilla), Sevilla, Spain.
    Petricevic, Branka
    Medizinische Abteilung, Zentrum für Onkologie und Hämatologie mit Ambulanz und alliativstation Wilhelminenspital, Vienna, Austria.
    Dambrosio, Mario
    epartment of Clinical Oncology, Clinica San Carlo, Milan, Italy.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Kountourakis, Pantelis
    Medical Oncology Department, Bank of Cyprus Oncology Centre, Nicosia, Cyprus.
    Kopecky, Jindrich
    Department of Clinical Oncology, University Hospital, Charles University-Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czechia.
    Kuhar, Cvetka Grašič
    Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
    Popovic, Lazar
    Oncology Institute of Vojvodina, University of Novi Sad, Novi Sad, Serbia.
    Chilingirova, Nataliya P.
    University Specialized Hospital for Active Treatment in Oncology, Medical Oncology Clinic, Sofia, Bulgaria; Medical University Pleven, Pleven, Bulgaria.
    Zarkavelis, George
    Department of Medical Oncology, University Hospital of Ioannina, Ioannina, Greece.
    de Mello, Ramon Andrade
    Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
    Plavetić, Natalija Dedić
    University Hospital Centre, Zagreb Department of Oncology, School of Medicine, University of Zagreb, Zagreb, Croatia.
    Christopoulos, Christos
    Service de Radiothérapie Oncologique, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Montfermeil, France.
    Mostert, Bianca
    Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
    Goffin, John R.
    Department of Oncology, McMaster University Juravinski Cancer Centre, Hamilton, ON, Canada.
    Tzachanis, Dimitiros
    Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, United States.
    Saraireh, Haytham Hamed
    Radiation Oncology Department, Jordanian Royal Medical Services, Amman, Jordan.
    Ma, Fei
    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
    Pavese, Ida
    Service d'Oncologie, GHT Grand Paris Nord-Est, Montfermeil, France.
    Tolia, Maria
    Department of Radiotherapy, School of Medicine, University of Crete, Heraklion, Greece.
    Synthesis of Recommendations From 25 Countries and 31 Oncology Societies: How to Navigate Through Covid-19 Labyrinth2020In: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 10, article id 575148Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak.

    Methods: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies.

    Results: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis.

    Conclusions: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.

  • 12.
    Karakatsanis, Andreas
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Breast Unit, Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Charalampoudis, Petros
    Oncoplastic Breast Unit, University College London Hospitals, London, UK.
    Pistioli, Lida
    Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Di Micco, Rosa
    Breast Unit, San Raffaele University Hospital, Milan, Italy.
    Foukakis, Theodoros
    Department of Oncology-Pathology, Karolinska Institute Stockholm, Stockholm, Sweden; Breast Centre, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Axillary evaluation in ductal cancer in situ of the breast: challenging the diagnostic accuracy of clinical practice guidelines2021In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 108, no 9, p. 1120-1125Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Staging of the axilla is not routine in ductal cancer in situ (DCIS) although invasive cancer is observed in 20-25 per cent of patients at final pathology. Upfront sentinel lymph node dissection (SLND) is advocated in clinical practice guidelines in certain situations. These include expected challenges in subsequent SLN detection and when the risk for invasion is high. Clinical practice guidelines are, however, inconsistent and lead to considerable practice variability.

    METHODS: Clinical practice guidelines for upfront SLND in DCIS were identified and applied to patients included in the prospective SentiNot study. These patients were evaluated by six independent, blinded raters. Agreement statistics were performed to assess agreement and concordance. Receiver operating characteristic curves were constructed, to assess guideline accuracy in identifying patients with underlying invasion.

    RESULTS: Eight guidelines with relevant recommendations were identified. Interobserver agreement varied greatly (kappa: 0.23-0.9) and the interpretation as to whether SLND should be performed ranged from 40-90 per cent and with varying concordance (32-88 per cent). The diagnostic accuracy was low with area under the curve ranging from 0.45 to 0.55. Fifty to 90 per cent of patients with pure DCIS would undergo unnecessary SLNB, whereas 10-50 per cent of patients with invasion were not identified as 'high risk'. Agreement across guidelines was low (kappa = 0.24), meaning that different patients had a similar risk of being treated inaccurately.

    CONCLUSION: Available guidelines are inaccurate in identifying patients with DCIS who would benefit from upfront SLNB. Guideline refinement with detailed preoperative work-up and novel techniques for SLND identification could address this challenge and avoid overtreatment.

  • 13.
    Karakatsanis, Andreas
    et al.
    Department for Surgical Sciences, Faculty of Medicine, Uppsala University and Section for Breast Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Foukakis, Theodoros
    Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Per
    Sahlgrenska Academy / Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mamounas, Eleftherios
    Orlando Health UF Health Cancer Center, Orlando FL, USA.
    Chagpar, Anees
    Yale University School of Medicine, New Haven CT, USA.
    Boyages, John
    Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
    Rubio, Isabel
    Navarra University Clinic, Madrid, Spain.
    Naume, Bjørn
    Oslo University Hospital, Oslo, Norway.
    Mauri, Davide
    Faculty of Medicine, University of Ioannina, Ioannina, Greece.
    van der Wall, Elsken
    University Medical Center Utrecht, Utrecht, Netherlands.
    Shah, Chirag
    Taussig Cancer Institute, Cleveland Clinic, Cleveland OH, USA.
    Kwong, Ava
    The University of Hong Kong, Queen Mary and Tung Wah Hospital and The University of Hong Kong-ShenZhen Hospital, Hong Kong.
    McAuliffe, Priscilla
    Women's Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh, UPMC Hillman Cancer Center, Division of Surgical Oncology, Department of Surgery, Pittsburgh PA, USA.
    Gentilini, Oreste
    IRCCS San Raffaele, Milan, Italy.
    Ignatiadis, Michail
    Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium.
    Schlichting, Ellen
    Oslo University Hospital, Oslo, Norway.
    Zgajnar, Janez
    Institute of Oncology Ljubljana, Ljubljana, Slovenia.
    Meani, Francesco
    Lugano Hospital, Lugano, Switzerland.
    Tasoulis, Marios Konstantinos
    Royal Marsden Hospital, London, United Kingdom.
    Whitworth, Pat
    Nashville Breast Center, Nashville TN, USA.
    Weber, Walter
    Basel University Hospital, Basel, Switzerland.
    Charalampoudis, Petros
    University College London Hospitals, London, United Kingdom.
    Gulluoglu, Bahadir
    Marmara University Hospital, Istanbul, Turkey.
    Pistioli, Lida
    Institute of Clinical Sciences- Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Tvedskov, Tove Filtenborg
    Rigshospitalet, Copenhagen, Denmark.
    Leidenius, Marjut
    Helsinki University Central Hospital, Helsinki, Finland.
    Mann, Bruce
    The University of Melbourne, Melbourne, Australia.
    Witkamp, Arjen
    University Medical Center Utrecht, Utrecht, Netherlands.
    Wyld, Lynda
    University of Sheffield, Sheffield, United Kingdom.
    di Micco, Rosa
    IRCCS San Raffaele, Milan, Italy.
    Markopoulos, Christos
    National and Kapodistrian University, Athens, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wärnberg, Fredrik
    Uppsala University, Uppsala, Sweden.
    Axillary Staging in the Setting of a Preoperative Diagnosis of Ductal Cancer In Situ (DCIS): Results of an International Expert Panel and a Critical Guideline Performance Using Frequentist and Bayesian Analysis2020In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 27, no Suppl. 2, p. S337-S338Article in journal (Other academic)
    Abstract [en]

    Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB.

    Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion.

    Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB in 41.3/61.4%, whereas individual rates ranged from 11 to 100%. Agreement among panelists was low (kappa=0.37). In multivariate regression analysis for the entire panel, type of surgery was the most common determinant, (simple WLE=less, OPBCS=more and Mx=constant for SLNB), followed by symptomatic diagnosis and DCIS size. Most (26) members had a clear decision-making pattern regarding SLND, based mainly on DCIS size and type of surgery. Individual decision-making performed modestly in identifying patients with underlying invasion (AUC range 0,47-0,59), resulting mainly in overtreatment in 44-77% of patients. The panel performed similarly by majority (AUC 0,5) and by consensus (AUC 0,55) but “undertreated” 60-75% of patients with invasion, failing to identify them as "high-risk." After the recognition of different decision-making patterns, panelists were divided in subgroups with similar decision-making pattern. Analysis identified subgroups with difference in SLNB rate but not with better AUC. The disagreement among panelists in the same subgroups was significant, not only regarding which patients should undergo SLNB, but also on what factors that recommendation was based on. Eight guidelines with relevant recommendations were identified [USA (ASCO/NCCN), Europe (ESMO), Sweden, Denmark, UK, Netherlands and Italy, retrieval date May 2019]. Agreement among raters for each guideline separately varied (kappa: 0.23-0.9). Interpretation as to whether SLNB should be performed ranged widely (40-90%) and with varying concordance (32-88%). No guideline demonstrated accuracy (AUC range 0.45-0.55). Overtreatment risk was high (50-90%), whereas 10-50% of patients with invasion were not identified as “high- risk.” Agreement across guidelines was low (kappa=0.24), meaning that different patients had similar risk to be treated inaccurately, regardless of which guideline was examined.

    Conclusions: Individualized decision-making and guideline interpretation may be highly subjective and with low accuracy in terms of prediction of invasive disease, resulting in almost random risk for over- or undertreatment of the axilla in patients with DCIS. This suggests that current views and guidelines should be challenged. More accurate preoperative workup and novel techniques to allow for delayed SLNB may be of value in this setting.

  • 14.
    Karihtala, P.
    et al.
    Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
    Valachis, A
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept. of Oncology.
    Tuxen, M.
    Oncology, Herlev and Gentofte Hospital, Herlev, Denmark.
    Geisler, J.
    Oncology Dept., Akershus universitetssykehus HF, Lorenskog, Norway.
    Current treatment landscape of HR+/HER2-advanced breast cancer in the Nordics: A modified Delphi study2022In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 33, no Suppl. 3, p. S218-S218Article in journal (Other academic)
    Abstract [en]

    Background: The aim of this Delphi study was to assess current perspectives on HR+/HER2- advanced breast cancer (aBC) treatment strategies among Nordic BC oncologists, and to gain broader understanding of the uptake and implementation of novel treatments.

    Methods: A modified, three round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection and questionnaires development. The questionnaires covered clinically relevant topics related to HR+/HER2- aBC treatment: treatment patterns in different lines of therapy (first- (1L), second- (2L) and third-line (3L)), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement.

    Results: In total 28 panelists participated in the study. In rounds one and two, 14 and 21 questions reached consensuses, respectively. Thirteen non-consensus reaching questions were reposted in round three, where 10 reached consensus. Overall, topics that reached a high consensus level included: treatment approaches in 1L and 2L treatment setting for HR+/HER2- aBC, treatment of oligometastatic disease, visceral crisis and brain metastases, and age-related treatment considerations. No consensus was reached for aspects regarding 3L therapy and de novo aBC. Endocrine therapy (ET) combined with CDK4/6i was the treatment of choice for both 1L and 2L therapy. Regarding implementation of clinical guidelines, a discrepancy was observed between treatments recommended in guidelines and those used in clinical practice, especially in cases where novel treatments were proposed.

    Conclusions: Endocrine therapy combined with a CDK4/6i is the frontline treatment choice for HR+/HER2- aBC in the Nordics. Observed discrepancies between international clinical guidelines and practice are partly due to difference in the availability of novel treatment strategies that might lead to differences in clinical experience in the Nordics. The lack of consensus might reflect limited evidence on these topics and the need for collaborative research efforts. Written on behalf of Nordic Delphi Panellist group.

  • 15.
    Kastora, Stavroula Lila
    et al.
    University College London, UCL EGA Institute for Women's Health, London, United Kingdom; School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
    Holmquist, Alexander
    Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Rocco, Nicola
    Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy; G.RE.T.A. Group for Reconstructive and Therapeutic Advancements, Milan, Naples, and Catania, Italy.
    Meattini, Icro
    Department of Experimental and Clinical Biomedical Sciences M. Serio, University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Florence University Hospital, Florence, Italy.
    Somaiah, Navita
    Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom.
    Peled, Anne
    Sutter Health California Pacific Medical Center, San Francisco, USA.
    Chatterjee, Abhishek
    Division of Surgical Oncology and Plastic Surgery, Tufts Medical Center, Boston, Massachusetts, USA.
    Catanuto, Giuseppe
    G.RE.T.A. Group for Reconstructive and Therapeutic Advancements, Milan, Naples, and Catania, Italy; Humanitas, Institute Clinico Catanese-Misterbianco, Catania, Italy.
    Tasoulis, Marios Konstantinos
    Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom; Breast Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.
    Nava, Maurizio Bruno
    Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerpen, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerpen, Belgium.
    Poortmans, Philip
    Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerpen, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerpen, Belgium.
    Pusic, Andrea
    Division of Plastic and Reconstructive Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
    Masannat, Yazan
    School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom; Aberdeen Royal Infirmary, Breast Surgery, NHS Grampian, Aberdeen, United Kingdom.
    Karakatsanis, Andreas
    Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden; Section for Breast Surgery, Department of Surgery, Uppsala University Hospital (Akademiska), Uppsala, Sweden.
    Outcomes of Different Quality of Life Assessment Modalities After Breast Cancer Therapy: A Network Meta-analysis2023In: JAMA Network Open, E-ISSN 2574-3805, Vol. 6, no 6, article id e2316878Article, review/survey (Refereed)
    Abstract [en]

    IMPORTANCE: Improvement in clinical understanding of the priorities of patients with breast cancer (BC) regarding postoperative aesthetic outcomes (AOs) is needed.

    OBJECTIVE: To assess expert panel and computerized evaluation modalities against patient-reported outcome measures (PROMs), the gold standard of AO assessment, in patients after surgical management of BC.

    DATA SOURCES: Embase, MEDLINE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were interrogated from inception through August 5, 2022. Search terms included breast conserving AND aesthetic outcome AND breast cancer. Ten observational studies were eligible for inclusion, with the earliest date of database collection on December 15, 2022.

    STUDY SELECTION: Studies with at least 1 pairwise comparison (PROM vs expert panel or PROM vs computerized evaluation with Breast Cancer Conservation Treatment cosmetic results [BCCT.core] software) were considered eligible if they included patients who received BC treatment with curative intent. Studies reporting solely on risk reduction or benign surgical procedures were excluded to ensure transitivity.

    DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted study data with an independent cross-check from a third reviewer. The quality of included observational studies was assessed using the Newcastle-Ottawa Scale, and the level of evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Confidence in network meta-analysis results was analyzed with the Confidence in Network Meta-analysis semiautomated tool. Effect size was reported using random-effects odds ratios (ORs) and cumulative ratios of ORs with 95% credibility intervals (CrIs).

    MAIN OUTCOMES AND MEASURES: The primary outcome of this network meta-analysis was modality (expert panel or computer software) discordance from PROMs. Four-point Likert responses across PROMs, expert panel assessment, and BCCT.core evaluation of AOs were assessed.

    RESULTS: A total of 10 observational studies including 3083 patients (median [IQR] age, 59 [50-60] years; median [range] follow-up, 39.0 [22.5-80.5] months) with reported AOs were assessed and homogenized in 4 distinct Likert response groups (excellent, very good, satisfactory, and bad). Overall network incoherence was low (χ22 = 0.35; P = .83). Overall, panel and software modalities graded AO outcomes worse than PROMs. Specifically, for excellent vs all other responses, the panel to PROM ratio of ORs was 0.30 (95% CrI, 0.17-0.53; I2 = 86%) and the BCCT.core to PROM ratio of ORs was 0.28 (95% CrI, 0.13-0.59; I2 = 95%), while the BCCT.core to panel ratio of ORs was 0.93 (95% CrI, 0.46-1.88; I2 = 88%).

    CONCLUSIONS AND RELEVANCE: In this study, patients scored AOs higher than both expert panels and computer software. Standardization and supplementation of expert panel and software AO tools with racially, ethnically, and culturally inclusive PROMs is needed to improve clinical evaluation of the journey of patients with BC and to prioritize components of therapeutic outcomes.

  • 16.
    Kofteridis, Diamantis P.
    et al.
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Andrianaki, Angeliki M.
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Maraki, Sofia
    Department of Clinical Microbiology, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Mathioudaki, Anna
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Plataki, Marina
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Alexopoulou, Christina
    Department of Intensive Care Unit, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Ioannou, Petros
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Samonis, George
    Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Treatment pattern, prognostic factors, and outcome in patients with infection due to pan-drug-resistant gram-negative bacteria2020In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 39, no 5, p. 965-970Article in journal (Refereed)
    Abstract [en]

    The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.

  • 17.
    Kofteridis, Diamantis P.
    et al.
    Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Valachis, Antonis
    Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden; University of Uppsala, Uppsala, Sweden.
    Dimopoulou, Dimitra
    Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Andrianaki, Angeliki M.
    Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Christidou, Athanasia
    Clinical Microbiology, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Maraki, Sofia
    Clinical Microbiology, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Spernovasilis, Nikolaos A.
    Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
    Samonis, George
    Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, 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.

  • 18. Kornalijnslijper-Altena, Renske
    et al.
    Andersson, Anne
    Brandberg, Yvonne
    Kessler, Luisa Edman
    Elinder, Ellinor
    Hartman, Johan
    Hellstrom, Mats
    Johansson, Hemming
    Killander, Fredrika
    Linderholm, Barbro Kristina
    Lindman, Henrik
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wennstig, Anna Karin
    Xie, Hanjing
    Hatschek, Thomas
    Bergh, Jonas C. S.
    PREDIX II HER2: Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC)2020In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 38, no 15 Suppl., article id TPS605Article in journal (Other academic)
    Abstract [en]

    Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy.

    Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007.

  • 19.
    Lampropoulos, Konstantinos
    et al.
    University of Patras, Department of Electrical and Computer Engineering, Patras, Greece.
    Kosmidis, Thanos
    CareAcross Research, CareAcross LTD, London, United Kingdom.
    Autexier, Serge
    German Research Center for Artificial Intelligence (DFKI), RD Cyber-Physical Systems, Bremen, Germany.
    Savic, Milos
    University of Novi Sad, Division of Informatics, Faculty of Sciences, Novi Sad, Serbia.
    Athanatos, Manos
    Institute of Computer Science, Foundation for Research and Technology - Hellas, Heraklion, Crete, Greece.
    Kokkonidis, Miltiadis
    International S.A., Research and Innovation Development INTRASOFT, Luxembourg, Luxembourg.
    Koutsouri, Tzortzia
    SPHYNX Technology Solutions AG, SPHYNX Research, Zug, Switzerland.
    Vizitiu, Anamaria
    Transilvania University of Brasov, Department of Automation and Information Technology, Brasov, Romania; Advanta, Siemens SRL, Brasov, Romania.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Padron, Miriam Quintero
    Atos S.A.E, Atos Research and Innovation, Madrid, Spain.
    ASCAPE: An open AI ecosystem to support the quality of life of cancer patients2021In: 2021 IEEE 9th International Conference on Healthcare Informatics (ICHI), IEEE Computer Society, 2021, p. 301-310Conference paper (Refereed)
    Abstract [en]

    The latest cancer statistics indicate a decrease in cancer-related mortality. However, due to the growing and ageing population, the absolute number of people living with cancer is set to keep increasing. This paper presents ASCAPE, an open AI infrastructure that takes advantage of the recent advances in Artificial Intelligence (AI) and Machine Learning (ML) to support cancer patients' quality of life (QoL). With ASCAPE health stakeholders (e.g. hospitals) can locally process their private medical data and then share the produced knowledge (ML models) through the open AI infrastructure.

  • 20.
    Löfgren, David
    et al.
    Örebro University, School of Medical Sciences. Department of Oncology.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Olivecrona, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurosurgery.
    Older meningioma patients: a retrospective population-based study of risk factors for morbidity and mortality after neurosurgery.2022In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, p. 2987-2997Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time.

    METHODS: In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999-2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mortality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma.

    RESULTS: The final study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes.

    CONCLUSIONS: Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.

  • 21.
    Löfgren, David
    et al.
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Medicine & Health, Örebro University, Örebro, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Olivecrona, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurosurgery.
    Risk for morbidity and mortality after neurosurgery in older patients with high grade gliomas: a retrospective population based study2022In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 22, no 1, article id 805Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although high grade gliomas largely affect older patients, current evidence on neurosurgical complications is mostly based on studies including younger study populations. We aimed to investigate the risk for postoperative complications after neurosurgery in a population-based cohort of older patients with high grade gliomas, and explore changes over time.

    METHODS: In this retrospective study we have used data from the Swedish Brain Tumour Registry and included patients in Sweden age 65 years or older, with surgery 1999-2017 for high grade gliomas. We analysed number of surgical procedures per year and which factors contribute to postoperative morbidity and mortality.

    RESULTS: The study included 1998 surgical interventions from an area representing 60% of the Swedish population. Over time, there was an increase in surgical interventions in relation to the age specific population (p < 0.001). Postoperative morbidity for 2006-2017 was 24%. Resection and not having a multifocal tumour were associated with higher risk for postoperative morbidity. Postoperative mortality for the same period was 5%. Increased age, biopsy, and poor performance status was associated with higher risk for postoperative mortality.

    CONCLUSIONS: This study shows an increase in surgical interventions over time, probably representing a more active treatment approach. The relatively low postoperative morbidity- and mortality-rates suggests that surgery in older patients with suspected high grade gliomas can be a feasible option. However, caution is advised in patients with poor performance status where the possible surgical intervention would be a biopsy only. Further, this study underlines the need for more standardised methods of reporting neurosurgical complications.

  • 22. 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.

  • 23.
    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.

  • 24.
    Matikas, Alexios
    et al.
    Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Zerdes, Ioannis
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Lövrot, John
    Breast Center, Theme Cancer, KarolinskaDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Sifakis, Emmanouil
    Breast Center, Theme Cancer, Karolinska UniDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Richard, Francois
    Department of Oncology, KU Leuven, Leuven, Flanders, Belgium.
    Sotiriou, Christos
    Department of Medical Oncology, Institute Jules Bordet, Brussels, Belgium.
    Rassidakis, Georgios
    Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
    Bergh, Jonas
    Breast Center, Theme Cancer, Karolinska University Hospital, 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, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    PD-1 protein and gene expression as prognostic factors in early breast cancer2020In: ESMO Open, E-ISSN 2059-7029, Vol. 5, no 6, article id e001032Article in journal (Refereed)
    Abstract [en]

    Background: There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study's aim was to comprehensively investigate it.

    Methods: The study consisted of three parts: a correlative analysis of PD-1 protein and gene expression from an original patient cohort of 564 patients with early BC; a systematic review and trial-level meta-analysis on the association between PD-1 protein expression and disease-free survival/overall survival (OS) in early BC; and a pooled gene expression analysis from publicly available transcriptomic datasets regarding PDCD1 expression.

    Results: In the study cohort, PD-1 protein, but not gene expression, was associated with improved OS (HRadj=0.73, 95% CI 0.55 to 0.97, p=0.027 and HRadj=0.88, 95% CI 0.68 to 1.13, p=0.312, respectively). In the trial-level meta-analysis, PD-1 protein expression was not found to be statistically significantly associated with outcomes in the overall population. Finally, in the pooled gene expression analysis, higher PDCD1 expression was associated with better OS in multivariable analysis in the entire population (HRadj=0.89, 95% CI 0.80 to 0.99, p=0.025) and in basal-like tumours.

    Conclusions: PD-1 protein and gene expression seem to be promising prognostic factors in early BC. Standardisation of detection and assessment methods is of utmost importance.

  • 25.
    Mauri, D.
    et al.
    Department of Medical Oncology, University Hospital of Ioannina, Ioannina, Greece; Oncology, EMEKEN, Ioannina, Greece.
    Kamposioras, K.
    Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom.
    Tzachanis, D.
    Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom.
    Tolia, M.
    Department of Radiotherapy/Radiation Oncology, University of Thessaly, Faculty of Medicine, Larissa, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Dambrosio, M.
    Division of Medical Oncology, Clinica San Carlo, Paderno Dugnano, Lombardia, Italy.
    Alongi, F.
    Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, University of Brescia, Verona, Italy.
    De Mello, R. A.
    Medicine, Univ Porto, Porto, Portugal; Medical Oncology/Research Center, Jorge Valente Hospital, Institute of Oncology, Salvador, Brazil.
    Lövey, J.
    Center of Radiotherapy, National Institute of Oncology, Department of Oncology, Semmelweis University, Budapest, Hungary.
    Anthoney, A.
    Department of Medical Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
    Christopoulos, C.
    Service de Radiothérapie Oncologique, Groupe Hospitalier Intercommunal le Raincy-Montfermeil, Montfermeil, Île-de-France, France.
    Saraireh, H. H.
    Radiation Oncology Department, King Hussein Medical Center, Jordanian Royal Medical Services, Amman, Jordan.
    Kountourakis, P.
    Medical Oncology Department, Bank of Cyprus Oncology Center, Strovolos, Cyprus.
    Kampletsas, E.
    Medical Oncology, University of Ioannina School of Medicine, Ioannina, Greece.
    Tsali, L.
    Section of Evidence Based Medicine, PACMeR, Athens, Greece.
    Tsakiridis, T.
    Radiation Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada.
    Kosovitsas, I.
    Department of Informatics, University of Pireaus, Pireas, Greece.
    Soukovelos, A.
    Section of Internet in Medicine, PACMeR Athens, Athens, Greece.
    Lymperatou, D.
    Section of Internet in Medicine, PACMeR Athens, Athens, Greece.
    Polyzos, N.
    Department of Reproductive Medicine, Dexeus University Hospital, Barcelona, Spain.
    Zarkavelis, G.
    Medical Oncology, University Hospital of Ioannina, Ioannina, Greece.
    Patient and family support in the era of fake e-medicine: Food for thought from an international consensus panel2020In: ESMO Open, E-ISSN 2059-7029, Vol. 5, no 2, article id e000696Article in journal (Refereed)
  • 26.
    Mauri, Davide
    et al.
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Kamposioras, Konstantinos
    Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
    Matthaios, Dimitrios
    Department of Oncology, General Hospital of Rhodes, Rhodes, Greece.
    Tolia, Maria
    Department of Radiotherapy/Radiation Oncology, Faculty of Medicine, University of Crete, Heraklion, Greece.
    Nixon, Ioanna
    Scottish Sarcoma Network (SSN) UK Chair NCRI HN Epidemiology and Survivorship Subgroup, The Beatson West of Scotland Cancer Centre, Glasgow, UK.
    Dambrosio, Mario
    Department of Medical Oncology, Clinica San Carlo, Paderno Dugnano, Italy.
    Zarkavelis, Georgios
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Papadimitriou, Konstantinos
    University Hospital of Antwerp, Antwerp, Belgium.
    Petricevic, Branka
    Department of Hematology and Oncology, Klinik Ottakring, Vienna, Austria.
    Kountourakis, Pantelis
    Medical Oncology Department, Bank of Cyprus Oncology Centre, Nicosia, Cyprus.
    Kopecky, Jindrich
    Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
    Kuhar, Cvetka Grašič
    Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
    Popovic, Lazar
    Medical Oncology Department, Oncology Institute of Vojvodina, University of Novi Sad, Novi Sad, Serbia.
    Chilingirova, Nataliya P.
    Medical Oncology Clinic at Specialized Hospital for Active Treatment in Oncology, University Pleven, Sofia, Bulgaria.
    De Mello, Ramon Andrade
    Department of Biomedical Sciences & Medicine, University of Algarve, Faro, Portugal; Precision Oncology Group, Federal University of São Paulo (UNIFESP), & Nine of July University (UNINOVE), São Paulo, Brazil.
    Plavetic, Natalija Dedic
    Department of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia.
    Katsanos, Konstantinos
    Department of Gastroenterology, University Hospital of Ioannina, Ιoannina, Greece.
    Mostert, Bianca
    Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
    Alongi, Filippo
    Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Verona, Italy; University of Brescia, Brescia, Italy.
    de Bari, Berardino
    Hospitalier Neuchâtelois, La Chaux-de-Fonds, Switzerland.
    Corradini, Stefanie
    Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
    Kampletsas, Eleytherios
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Gazouli, Ioanna
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Gkoura, Stefania
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Amylidi, Anna-Lea
    Department of Medical Oncology, University of Ιoannina, Ιoannina, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach2022In: Oncology Research and Treatment, ISSN 2296-5270, E-ISSN 2296-5262, Vol. 45, no 4, p. 216-220Article in journal (Refereed)
    Abstract [en]

    Background: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge.

    Summary: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions.

    Key Messages: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

  • 27.
    Mauri, Davide
    et al.
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Evidence Based Department, PACMeR Athens, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Tsali, Lampriani
    Evidence Based Department, PACMeR Athens, Greece.
    Polyzos, Nikolaos P.
    Hospital Universitari Dexeus, Barcelona, Spain.
    Valachis, Antonis
    Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
    Zafeiria, Georgia
    Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Kalopita, Konstantina
    Department of Anaesthesiology and Pain Medicine, “Alexandra” General Hospital, Athens, Greece.
    Tsiara, Anna
    Department of Medical Oncology, University of Athens, Greece.
    Yerolatsite, Melina
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Zarkavelis, Georgios
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Kampletsas, Eleftherios
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Mouzaki, Ioanna
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Ntellas, Panagiotis
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Filis, Panagiotis
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Pentheroudakis, Georgios
    Department of Medical Oncology, University Hospital of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.
    Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies2019In: Journal of B.U.ON. : official journal of the Balkan Union of Oncology, ISSN 2241-6293, 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.

  • 28.
    Mauri, Davide
    et al.
    Dept of Medical Oncology, University of Ιoannina, Greece.
    Tzachanis, Dimitrios
    UCSD/Moores Cancer Center, La Jolla CA, USA.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept of Oncology.
    Kamposioras, Konstantinos
    Dept of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
    Tolias, Maria
    Dept of Radiotherapy/Radiation Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University Hospital of Larisa, Biopolis, Larisa, Greece.
    Dambrosio, Mario
    Dept of Medical Oncology, Clinica San Carlo, Paderno Dugnano, Milan, Italy.
    Zarkavelis, Georgios
    Dept of Medical Oncology, University of Ιoannina, Greece.
    Gkoura, Stefania
    Dept of Medical Oncology, University of Ιoannina, Greece.
    Gazouli, Ioanna
    Dept of Medical Oncology, University of Ιoannina, Greece.
    De Lorenzo, Francesco
    FAVO (Federation of Oncology Volunteer Associations), Roma, Italy.
    Apostolidis, Kathi
    ECPC (European Cancer Patients Coalition), Brussels, Belgium.
    Behind the numbers and the panic of a viral pandemic: fixed restrictive oncology guidance may jeopardize patients' survival2020In: Balkan Union of Oncology. Journal, ISSN 1107-0625, Vol. 25, no 3, p. 1277-1280Article in journal (Refereed)
    Abstract [en]

    To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of tele-health services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits.

    Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening,follow-up and radical surgeries increase patients' risk of developing metastatic disease.

    A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients' outcomes.

    A present international oncologists' panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.

  • 29.
    Mauri, Davide
    et al.
    Department Medical Oncology, University Hospital of Ioannina, Ioannina, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department Medical Oncology.
    Tolia, Maria
    Department. Radiation Oncology, University Hospital of Heraklion, Crete, Greece.
    COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information2022In: Reviews on recent clinical trials, ISSN 1574-8871, E-ISSN 1876-1038, Vol. 17, no 1, p. 11-14Article in journal (Refereed)
    Abstract [en]

    Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support.

    Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations.

    Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries.

    Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population.

    Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

  • 30.
    Mauri, Davide
    et al.
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Zafeiri, Georgia
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Yerolatsite, Melina
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Tsali, Lampriani
    Department of Internal Medicine, General Hospital of Arta, Arta, Greece.
    Zarkavelis, Georgios
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Tsiara, Anna
    Department of Medical Oncology, Alexandra General Hospital, Athens, Greece.
    Polyzos, Nikolaos P.
    Hospital Universitari Dexeus, Barcelona, Spain.
    Valachis, Antonis
    Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
    Kalopita, Konastantina
    Department of Anaesthesiology and Pain Medicine, Alexandra General Hospital, Athens, Greece.
    Kampletsas, Eleftherios
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Papadaki, Alexandra
    Department of Medical Oncology, University Hospital of Ioannina, Greece; EMEKEN, Ioannina, Greece.
    Peponi, Evangelia
    Department of Radiotherapy, University Hospital of Ioannina, Greece.
    Kapoulitsa, Fani
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Filis, Panagiotis
    Department of Medical Oncology, University Hospital of Ioannina, Greece.
    Pentheroudakis, Georgios
    Department of Medical Oncology, University Hospital of Ioannina, 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.

  • 31.
    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.

  • 32.
    Mokhtary, Arezo
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Karakatsanis, Andreas
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Mammographic Density Changes over Time and Breast Cancer Risk: A Systematic Review and Meta-Analysis2021In: Cancers, ISSN 2072-6694, Vol. 13, no 19, article id 4805Article, review/survey (Refereed)
    Abstract [en]

    The aim of this meta-analysis was to evaluate the association between mammographic density changes over time and the risk of breast cancer. We performed a systematic literature review based on the PubMed and ISI Web of Knowledge databases. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for cohort studies or odds ratios (ORs) and 95% confidence interval using inverse variance method. Of the nine studies included, five were cohort studies that used HR as a measurement type for their statistical analysis and four were case-control or cohort studies that used OR as a measurement type. Increased breast density over time in cohort studies was associated with higher breast cancer risk (HR: 1.61; 95% CI: 1.33-1.96) whereas decreased breast density over time was associated with lower breast cancer risk (HR: 0.78; 95% CI: 0.71-0.87). Similarly, increased breast density over time was associated with higher breast cancer risk in studies presented ORs (pooled OR: 1.85; 95% CI: 1.29-2.65). Our findings imply that an increase in breast density over time seems to be linked to an increased risk of breast cancer, whereas a decrease in breast density over time seems to be linked to a lower risk of breast cancer.

  • 33.
    Mörth, Charlott
    et al.
    Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden; Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden; Cancercentrum, Mälarsjukhuset, 63188, Eskilstuna, Sweden.
    Valachis, Antonios
    Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden; Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Sabaa, Amal Abu
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Molin, Daniel
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Flogegård, Max
    Department of Internal Medicine, Falun General Hospital, Falun, Sweden.
    Enblad, Gunilla
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    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, 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.

  • 34.
    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.

  • 35.
    Naeser, Ylva
    et al.
    Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck laboratory, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Helgadottir, Hildur
    Department of Oncology, Karolinska University Hospital Solna, Solna, Sweden.
    Brandberg, Yvonne
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Hansson, Johan
    Department of Oncology, Karolinska University Hospital Solna, Solna, Sweden.
    Bagge, Roger Olofsson
    Sahlgrenska Cancer Center, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
    Elander, Nils O.
    Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Ingvar, Christian
    Department of Surgery, Clinical Sciences, Lund University, Lund, Sweden.
    Isaksson, Karolin
    Department of Surgery, Central Hospital Kristianstad, Kristianstad, Sweden; Department of Clinical Sciences, Surgery, Lund University, Lund, Sweden.
    Flygare, Petra
    Department of Oncology, Sundsvall County Hospital, Sundsvall, Sweden.
    Nilsson, Cecilia
    Department of Oncology, Hospital of Västmanland Västerås, Västerås, Sweden.
    Jakobsson, Frida
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Del Val Munoz, Olga
    Department of Oncology, Gävle County Hospital, Gävle, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Jansson, Malin
    Department of Surgical and perioperative sciences, Umeå University and Umeå University Hospital, Umeå, Sweden.
    Sparring, Charlotte
    Department of Dermatology, Skaraborg County Hospital, Skövde, Sweden.
    Ohlsson, Lars
    Department of Surgery, Karlstad County Hospital, Karlstad, Sweden.
    Dyrke, Ulf
    Department of Surgery, Falun County Hospital, Falun, Sweden.
    Papantoniou, Dimitrios
    Department of Oncology, Ryhov County Hospital, Jönköping, Sweden.
    Sundin, Anders
    Department of Surgical Sciences Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden.
    Ullenhag, Gustav J.
    Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck laboratory, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    TRIM study protocol: prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma2020In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 20, no 1, article id 1197Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only.

    METHODS: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.

    DISCUSSION: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.

    RESULTS: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.

    TRIAL REGISTRATION: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412.

  • 36.
    Naeser, Ylva
    et al.
    Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Helgadottir, Hildur
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Hansson, Johan
    Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Ingvar, Christian
    Department of Surgery, Clinical Sciences, Lund University, BMC, Lund, Sweden.
    Elander, Nils O.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Flygare, Petra
    Department of Oncology, Sundsvall County Hospital, Sundsvall, Sweden.
    Nilsson, Cecilia
    Department of Oncology, Hospital of Västmanland Västerås, Västerås, Sweden.
    Jakobsson, Frida
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Papantoniou, Dimitrios
    Department of Oncology, Ryhov County Hospital, Jönköping, Sweden.
    Nordin Danfors, Agneta
    Department of Oncology, Visby County Hospital,Visby, Sweden.
    Johansson, Hemming
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Sundin, Anders
    Department of Surgical Sciences Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden.
    Brandberg, Yvonne
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Ullenhag, Gustav J.
    Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study)2022In: Cancers, ISSN 2072-6694, Vol. 14, no 4, article id 1040Article in journal (Refereed)
    Abstract [en]

    The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/- whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients' HRQoL or levels of anxiety or depression.

  • 37.
    Nicolaescu, T-M
    et al.
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden; Center for Clinical Research of Uppsala University, Västmanland, Västerås Hospital, Västerås, Sweden; Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Abu Sabaa, A.
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Hedell, K.
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Morth, C.
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden; Center for Clinical Research of Uppsala University, Västmanland, Västerås Hospital, Västerås, Sweden; Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Center for Clinical Research of Uppsala University, Västmanland, Västerås Hospital, Västerås, Sweden .
    Enblad, G.
    Department of Immunology, Genetics, and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
    Prognostic relevance of pre-treatment c-reactive protein to albumin ratio in patients with diffuse large b cell lymphoma2022In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 33, no 7, p. S832-S832, article id 632PArticle in journal (Other academic)
    Abstract [en]

    Background: Previous studies have shown that a high level of pre-treatment C-reactive protein to albumin ratio (CAR) is associated with poor outcomes in patients with diffuse large B cell lymphoma (DLBCL). However, these were single-centre studies with a relatively small number of patients. The aim of our study was to further investigate the prognostic value of CAR in a larger cohort and whether the addition of CAR to the International Prognostic Index (IPI) would result in a better discriminatory ability.

    Methods: All adult patients treated 2000–2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n=414). The study population was divided into high respectively low CAR group using the Budczies et al.’s cut-off finder. The groups were compared in terms of differences in clinical characteristics, response to treatment and survival. The prognostic ability of IPI vs IPI plus CAR was compared by receiver-operating-characteristic curve (ROC), net reclassification improvement (NRI) and the integrated discrimination improvement index (IDI).

    Results: The high CAR group was associated with higher IPI score, lower performance status, high LDH, bulky disease and more advanced Ann Arbour stage. The high CAR group had a higher proportion of patients with progressive disease (24.2% vs 6.4%, p<0.001) and a lower proportion of patients with complete remission (61.5% vs 85.7%, p<0.01). The high CAR group had poorer 5-year OS (49% vs 70%; p<0.001) and EFS (45% vs 68%; p<0.001). After adjustment for BMI, bulky disease and IPI, high CAR values independently predicted poor OS (HR: 1.58, 95% CI 1.18–2.11; p=0.002) and EFS (HR: 1.57, 95% CI 1.18–2.10; p=0.002). When assessed by NRI, the addition of CAR to IPI seems to better identify patients with better prognosis compared with IPI alone. However, the area under the ROC curve and IDI did not show any significant improvement in model performance.

    Conclusions: CAR seems to be a useful prognostic biomarker in patients with DLBCL. Although the addition of CAR to IPI could identify some additional patients with better prognosis, the discriminatory ability of IPI was not improved. IPI remains the standard model for risk stratification in patients with DLBCL.

  • 38.
    Nikyar, Normehr
    et al.
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tegnelius, Eva
    Örebro University, School of Medical Sciences. Department of Oncology.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Adjuvant locoregional radiation therapy in breast cancer patients with pathologic complete response after neoadjuvant chemotherapy: A systematic review and meta-analysis2022In: Clinical and translational radiation oncology, ISSN 2405-6308, Vol. 33, p. 45-52Article, review/survey (Refereed)
    Abstract [en]

    Purpose: The aim of the present meta-analysis was to investigate the impact of adjuvant locoregional radiation therapy (LRRT) in breast cancer patients with clinical lymph node metastatic disease achieving ypN0 after neoadjuvant chemotherapy (NACT).

    Materials and methods: A systematic review of studies on PubMed was performed. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) into a fixed-effects model.

    Results: Thirteen studies were included in the meta-analysis. Adjuvant LRRT significantly reduced the risk of locoregional recurrence (LRR) in patients with N+ at diagnosis and ypN0 (HR 0.59; 95% CI 0.42-0.81). However, no statistically significant difference on disease-free survival (DFS) or overall survival (OS) was found.

    Conclusions: LRRT significantly reduced the risk of LRR in patients with ypN0 after NACT whereas no impact on DFS or OS was observed. The low level of evidence should be considered when interpreting the results in clinical practice.

  • 39.
    Ohlsson-Nevo, Emma
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Arvidsson Lindvall, Mialinn
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Hellerstedt Börjeson, Susanne
    Department of Public Health and Caring Sciences, Center for Clinical Research, Uppsala University, Uppsala, Sweden.
    Hagberg, Lars
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Wickberg, Åsa
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Duberg, Anna
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Digitally distributed Yoga Intervention in Breast Cancer Rehabilitation (DigiYoga CaRe): protocol for a randomised controlled trial2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 11, article id e065939Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Breast cancer is the most prevalent cancer among women. The treatment is extensive; in addition to surgery, various combinations of radiation therapy, chemotherapy and antibody and endocrine treatment can be applied. Cancer-related fatigue (CRF) is high in patients with breast cancer, peaking during chemotherapy, but may persist for several years. Physical activity has proven to be effective in reducing CRF in breast cancer rehabilitation, but many patients tend to be less active after the diagnosis. Yoga has a previously demonstrated effect on energy levels and digitally distributed yoga intervention can potentially increase accessibility in pandemic times and facilitate participation for patients susceptible to infection and those living far from organised rehabilitation opportunities. The purpose of this study, Digital Yoga Intervention in Cancer Rehabilitation (DigiYoga CaRe) is to investigate whether a 12-week digitally distributed yoga intervention can reduce CRF and stress, improve health-related quality of life (HRQL) and affect pro-inflammatory and metabolic markers in patients with breast cancer.

    METHODS AND ANALYSIS: This multicentre study will adopt a randomised controlled design including 240 persons after their breast cancer surgery. They will be randomised to a 12-week digitally distributed yoga intervention or to a control group. The intervention group practice yoga two times a week, one yoga class live-streamed to the patient's computer or mobile device and one prerecorded video class for self-training. The controls receive standardised care, gift cards for flowers and access to yoga video links after the data collection has ended. The primary analysis will be performed following the principle of intention to treat. Data will be collected by questionnaires, blood samples, accelerometers and interviews.

    ETHICS AND DISSEMINATION: The DigiYoga CaRe study was approved by the Regional Ethical Review Board in Lund. The final results of this study will be disseminated to conference, patient and public involvements and peer-reviewed publications.

    TRIAL REGISTRATION NUMBER: NCT04812652.

  • 40.
    Ohlsson-Nevo, Emma
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Arvidsson Lindvall, Mialinn
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Hellerstedt Börjesson, Susanne
    Uppsala University, Uppsala, Sweden.
    Hagberg, Lars
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Valachis, Antonis
    Örebro University, School of Medical Sciences.
    Wickberg, Åsa
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Duberg, Anna
    Örebro University, School of Health Sciences. Örebro University Hospital.
    A Digitally Distributed Yoga Intervention in Breast Cancer Rehabilitation (DigiYogaCaRe): Protocol for a Randomized Controlled Trial2023Conference paper (Other academic)
  • 41.
    Olsson Ladjevardi, Cecilia
    et al.
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Koliadi, Anthoula
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Rydén, Viktoria
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Inan El-Naggar, Ali
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Digkas, Evangelos
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Ullenhag, Gustav J.
    Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Predicting immune-related adverse events using a simplified frailty score in cancer patients treated with checkpoint inhibitors: A retrospective cohort study2023In: Cancer Medicine, E-ISSN 2045-7634, Vol. 12, no 12, p. 13217-13224Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Checkpoint inhibitors (CPIs) are in widespread clinical use. Little is known about which patients are at risk for developing toxicity. It is essential being able to identify patients with higher risk of experiencing immune-related adverse events (IRAEs) before initiation of CPI treatment to optimize treatment decisions and follow-up strategy. The aim of this study was to investigate whether a simplified frailty score based on performance status (PS), age, and comorbidity expressed as Charlson comorbidity index (CCI) could predict development of IRAEs.

    METHODS: We performed a retrospective cohort study at three Swedish centers. All patients (n = 596) treated with PD-L1 or PD-1 inhibitor for advanced cancer between January 2017 and December 2021 were included.

    RESULTS: In total, 361 patients (60.6%) were classified as nonfrail and 235 (39.4%) as frail. The most common cancer type was non-small cell lung cancer (n = 203; 34.1%) followed by malignant melanoma (n = 195; 32.7%). Any grade of IRAE occurred in 138 (58.7%) frail and in 155 (42.9%) non-frail patients (OR: 1.58; 95% CI: 1.09-2.28). Age, CCI, and PS did not independently predict the occurrence of IRAEs. Multiple IRAEs occurred in 53 (22.6%) frail and in 45 (12.5%) nonfrail patients (OR: 1.62; 95% CI: 1.00-2.64).

    DISCUSSION: In conclusion, the simplified frailty score predicted all grade IRAEs and multiple IRAEs in multivariate analyses whereas age, CCI, or PS did not separately predict development of IRAEs suggesting that this easy-to-use score may be of value in clinical decision making but a large prospective study is needed to assess its true value.

  • 42.
    Olsén, Johan Staby
    et al.
    Department of Oncology, General Hospital of Karlstad, Sweden.
    Estefan, Dalia
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Jakobsson, Frida
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Leif
    Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Johansson, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Predicting toxicity caused by high-dose-rate brachytherapy single boost for prostate cancer2022In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 14, no 1, p. 7-14Article in journal (Refereed)
    Abstract [en]

    Purpose: Treating localized prostate cancer (PC) with combination radiotherapy consisting of external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has been proven to result in better disease outcome than EBRT only. We aimed to evaluate the incidence of toxicities due to combination therapy and identify parameters correlated to acute or late urinary, rectal, and erectile toxicities.

    Material and methods: Data on symptoms and tumor/treatment parameters were collected from 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) and HDR-BT (14.5 Gy in one fraction) for localized PC, at the Örebro University Hospital. Urinary, rectal, and erectile symptoms were presented descriptively, and bivariate analyses for correlation between grade ≥ 2 toxicity and potential predictors were performed. To evaluate prognostic models, multivariable analyses were applied.

    Results: Urinary toxicity grade ≥ 2 was observed in 154 patients (47% of patients without pre-existing symptoms grade ≥ 2), of which 15 were grade 3. Rectal toxicity grade 2 was observed in 22 (6%) patients. Any grade erectile dysfunction was evident in all patients without pre-existing dysfunction (n = 103), whereas only 7 recovered completely. In bivariate analyses age was correlated with higher risk of acute urinary toxicity, and irradiated volume was associated with both urinary and rectal toxicities. However, we found no multivariable model of clinical and statistical significance to predict the risk of urinary or rectal toxicities.

    Conclusions: In our study cohort, the severity of toxicities was in general mild or moderate and temporary, whereas the incidence of severe toxicity was considerably low. Although we found no predictive models for toxicities, our findings are reassuring that this treatment approach as curative therapy for localized PC is well-tolerated.

  • 43.
    Paakkola, N.-M.
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karakatsanis, A.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Mauri, D.
    Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
    Foukakis, T.
    Department of Oncology-Pathology, Karolinska Institutet Stockholm, Stockholm, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis2021In: ESMO Open, E-ISSN 2059-7029, Vol. 6, no 6, article id 100289Article, review/survey (Refereed)
    Abstract [en]

    INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors.

    METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups.

    DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.

  • 44.
    Pantiora, Eirini
    et al.
    Department for Surgical Sciences, Uppsala University, Uppsala, Sweden; Section for Breast Surgery, Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Tasoulis, Marios Konstantinos
    Breast Surgery Unit, Royal Marsden NHS Foundation Trust, London, UK; Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Staffan
    Section for Breast Surgery, Department of Surgery, Västmanland Hospital, Västerås, Sweden; Centre for Clinical Research, Uppsala University, Västerås, Sweden.
    Kühn, Thorsten
    Department of Gynaecology and Obstetrics, Interdisciplinary Breast Centre, Hospital Esslingen, Esslingen, Germany.
    Karakatsanis, Andreas
    Department for Surgical Sciences, Uppsala University, Uppsala, Sweden; Section for Breast Surgery, Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Rubio, Isabel T.
    Breast Surgical Unit, Clinica Universidad de Navarra, Cancer Centre University of Navarra, Madrid, Spain.
    Evolution and refinement of magnetically guided sentinel lymph node detection in breast cancer: meta-analysis2023In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 110, no 4, p. 410-419Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD).

    METHODS: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach.

    RESULTS: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI ± BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI ± BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection.

    CONCLUSION: The performance of SPIO is comparable to that of RI ± BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

  • 45.
    Pellat, A.
    et al.
    Gastroenterology and digestive oncology Department, Hôpital Cochin, Paris, France.
    Grinda, T.
    Medical Oncology Dept., Institut Gustave Roussy, Villejuif, France.
    Prelaj, A.
    Department of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
    Cresta, P.
    Medical Oncology Dept., VHIO - Vall d’Hebron Institute of Oncology, Barcelona, Spain.
    Valachis, A
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dpt. of Oncology.
    Zerdes, I.
    Oncology-Pathology Department, Karolinska Institutet - Bioclinicum, Solna, Sweden.
    Branco, D. Martins
    Academic Trials Promoting Team (ATPT), Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium.
    Provenzano, L.
    Department of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
    Spagnoletti, A.
    Department of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
    Marta, G. Nader
    Academic Trials Promoting Team (ATPT), Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium.
    Wilson, B.
    Department of Oncology, Queen's University, Kingston ON, Canada.
    Montemurro, F.
    Investigative Clinical Oncology dept., IRCCS - Istituto di Candiolo - FPO, Turin, Italy.
    Castelo-Branco, L.
    Scientific and Medical Division, ESMO - European Society for Medical Oncology, Lugano, Switzerland.
    Pentheroudakis, G.
    Scientific and Medical Division, ESMO - European Society for Medical Oncology, Lugano, Switzerland.
    Delaloge, S.
    Breast Oncology Department, Institut Gustave Roussy, Villejuif, France.
    Koopman, M.
    Medical Oncology Department, UMC - University Medical Center Utrecht, Utrecht, Netherlands.
    Comprehensive mapping review of real-world evidence publications focusing on targeted therapies in solid tumors: A collaborative work from ESMO real-world data and Digital Health Working Group2023In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 34, no Suppl. 2, p. S925-S925, article id 16890Article in journal (Other academic)
    Abstract [en]

    Background: A growing body of real-world evidence (RWE) aims to better reflect outcomes of cancer patients treated in real-world settings. We aimed to conduct a first comprehensive mapping review of the RWE produced over the past 3 years in terms of tumor type, treatment strategies, setting, and data sources, focusing on targeted therapies (TT) in solid tumors.

    Methods: We conducted a systematic review in PubMed of RWE studies published between 01/2020 and 12/2022. We identified non-interventional studies using observational data, focusing on solid tumors exposure to targeted therapies, excluding immunotherapies. Abstract and full-text screening were performed by 11 independent reviewers.

    Results: A total of 7,774 publications were retrieved with 1,251 considered eligible and extracted. The number of publications per year progressively increased during this period (328 in 2020; 421 in 2021; 502 in 2022). Most studies (50%) were performed in Asia, followed by Europe (25%) and North America (17%). Only 8% of studies had patients treated in more than one country. Treatment effectiveness and safety were assessed in 71% and 42% of studies respectively. Main data sources were medical records.

    Conclusions: RWE publications on TT for solid tumors are heterogeneous and mostly rely on retrospective data such as medical records. Population-based and international studies are rare. Collaborative efforts towards international representativeness and the use of routinely collected and/or standardized data sources must be encouraged to increase the relevance and future quality of publications and their potential impact on oncology practice.

  • 46.
    Rodriguez-Wallberg, Kenny A.
    et al.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Nilsson, Hanna Pauline
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Bergh, Jonas
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Theme cancer, Karolinska Comprehensive Cancer Center and University Hospital, Stockholm, Sweden.
    Malmros, Johan
    Pediatric Theme Astrid Lindgren's Pediatric Hospital, Stockholm, Sweden.
    Ljungman, Per
    Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden; Division of Hematology, Department of Medicine Huddinge, Karolinska Institute, Huddinge, Sweden.
    Foukakis, Theodoros
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Theme cancer, Karolinska Comprehensive Cancer Center and University Hospital, Stockholm, Sweden.
    Stragliotto, Christina Linder
    Theme cancer, Karolinska Comprehensive Cancer Center and University Hospital, Stockholm, Sweden.
    Friman, Erika Isaksson
    Department of Oncology, Capio ST, Göran Hospital, Stockholm, Sweden.
    Linderholm, Barbro
    Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Andersson, Anne
    Department of Oncology, Norrlands University Hospital, Umeå, Sweden.
    Harrysson, Sara
    Department of Hematology, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden.
    Vennström, Lovisa
    Department of Hematology and Coagulation, Sahlgrenska University Hospital, Goteborg, Sweden.
    Frisk, Per
    Akademiska Hospital, Uppsala, Sweden.
    Mörse, Helena
    Center for Pediatric Oncology, Skåne University Hospital, Lund, Sweden.
    Eloranta, Sandra
    Department of Medicine, Karolinska Institute, Solna, Sweden; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden-a phase III randomised double-blinded placebo-controlled study2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 12, article id e078023Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.

    METHODS AND ANALYSIS: A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14-42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.

    ETHICS AND DISSEMINATION: This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.

    STUDY REGISTRATION: The National Institutional review board in Sweden dnr:2021-03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.

    TRIAL REGISTRATION NUMBER: NCT05328258; EudraCT number:2020-004780-71.

  • 47.
    Rosin, Justus
    et al.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Svegrup, Ella
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Zerdes, Ioannis
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital & Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
    Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis2023In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 201, no 2, p. 161-169Article, review/survey (Refereed)
    Abstract [en]

    INTRODUCTION: In light of the clinically meaningful results of the PI3K inhibitors in PIK3CA-mutated metastatic breast cancer (BC) patients, the reliable identification of PIK3CA mutations is of outmost importance. However, lack of evidence on the optimal site and timing of assessment, presence of temporal heterogeneity and analytical factors pose several challenges in clinical routine. We aimed to study the discordance rates of PIK3CA mutational status between primary and matched metastatic tumors.

    METHODS: A systematic literature search was performed in three different databases (Embase, Pubmed, Web of Science) and-upon screening-a total of 25 studies reporting PIK3CA mutational status both on primary breast tumors and their matched metastases were included in this meta-analysis. The random-effects model was used for pooled analyses of discordance of PIK3CA mutational status.

    RESULTS: The overall discordance rate of PIK3CA mutational status was 9.8% (95% CI, 7.0-13.0; n = 1425) and did not significantly differ within BC subtypes or metastatic sites. The change was bi-directional, more commonly observed from PIK3CA mutated to wild-type status (14.9%, 95% CI 11.8-18.2; n tumor pairs = 453) rather than the opposite direction (8.9%, 95% CI 6.1-12.1; n tumor pairs = 943).

    CONCLUSIONS: Our results indicate the need of obtaining metastatic biopsies for PIK3CA-mutation analysis and the possibility of testing of the primary tumor, in case a re-biopsy deemed non-feasible.

  • 48.
    Rydén, Viktoria
    et al.
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    El-Naggar, Ali Inan
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Koliadi, Anthoula
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Ladjevardi, Cecilia Olsson
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    Digkas, Evangelos
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden; Department of Oncology, Eskilstuna, Sweden.
    Valachis, Antonios
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Ullenhag, Gustav J
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
    The role of dacarbazine and temozolomide therapy after treatment with immune checkpoint inhibitors in malignant melanoma patients: A case series and meta-analysis2023In: Pigment Cell & Melanoma Research, E-ISSN 1755-148XArticle in journal (Refereed)
    Abstract [en]

    Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04-4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.

  • 49.
    Savic, Milos
    et al.
    Department of Mathematics and Informatics, Faculty of Sciences, University of Novi Sad Trg D. Obradovi ́ca 3, Novi Sad, Serbia.
    Kurbalija, Vladimir
    Department of Mathematics and Informatics, Faculty of Sciences, University of Novi Sad Trg D. Obradovi ́ca 3, Novi Sad, Serbia.
    Ilic, Mihailo
    Department of Mathematics and Informatics, Faculty of Sciences, University of Novi Sad Trg D. Obradovi ́ca 3, Novi Sad, Serbia.
    Ivanovic, Mirjana
    Department of Mathematics and Informatics, Faculty of Sciences, University of Novi Sad Trg D. Obradovi ́ca 3, Novi Sad, Serbia.
    Jakovetic, Dusan
    Department of Mathematics and Informatics, Faculty of Sciences, University of Novi Sad Trg D. Obradovi ́ca 3, Novi Sad, Serbia.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Autexier, Serge
    German Research Center for Artificial Intelligence GmbH, Cyber-Physical Systems Bremen, Germany.
    Rust, Johannes
    German Research Center for Artificial Intelligence GmbH, Cyber-Physical Systems Bremen, Germany.
    Kosmidis, Thanos
    Care Across Ltd, London, England.
    The Application of Machine Learning Techniques in Prediction of Quality of Life Features for Cancer Patients2023In: Computer Science and Information Systems, ISSN 1820-0214, Vol. 20, no 1, p. 381-404Article in journal (Refereed)
    Abstract [en]

    Quality of life (QoL) is one of the major issues for cancer patients. With the advent of medical databases containing large amounts of relevant QoL infor-mation it becomes possible to train predictive QoL models by machine learning (ML) techniques. However, the training of predictive QoL models poses several challenges mostly due to data privacy concerns and missing values in patient data. In this paper, we analyze several classification and regression ML models predicting QoL indicators for breast and prostate cancer patients. Three different approaches are employed for imputing missing values, and several settings for data privacy pre-serving are tested. The examined ML models are trained on datasets formed from two databases containing a large number of anonymized medical records of can-cer patients from Sweden. Two learning scenarios are considered: centralized and federated learning. In the centralized learning scenario all patient data coming from different data sources is collected at a central location prior to model training. On the other hand, federated learning enables collective training of machine learning models without data sharing. The results of our experimental evaluation show that the predictive power of federated models is comparable to that of centrally trained models for short-term QoL predictions, whereas for long-term periods centralized models provide more accurate QoL predictions. Furthermore, we provide insights into the quality of data preprocessing tasks (missing value imputation and differen-tial privacy).

  • 50.
    Schiza, Aglaia
    et al.
    Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjoldsvag 20, Uppsala, 751 85, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, 751 85, Sweden.
    Fredriksson, Irma
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Breast, Endocrine Tumours and Sarcoma, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
    Sund, Malin
    Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden; Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjoldsvag 20, Uppsala, 751 85, Sweden; Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    De Novo metastatic breast cancer in males versus females: a Swedish, population-based cohort study2023In: JNCI cancer spectrum, E-ISSN 2515-5091, Vol. 7, no 4, article id pkad050Article in journal (Refereed)
    Abstract [en]

    Current evidence on de novo metastatic breast cancer (dnMBC) is based on data from women. This Swedish, population-based cohort study compared the incidence over time and prognosis of dnMBC between sexes using data from the National Quality register for Breast Cancer. Joinpoint regression analysis was used to compare incidence trends in all stages (104,733 women, 648 men) and multivariate Cox regression analysis to investigate potential sex disparities in dnMBC prognosis (6005 women, 41 men). For both sexes, increased trends were evident for stages I-II with a stabilizing trend at the later years for women while stage III incidence remained stable. An increased trend for dnMBC in women, and to less extent in men, was observed. No difference in dnMBC overall survival between sexes was observed (HR : 1.24; 95% CI : 0.85-1.81). The comparable features in terms of incidence and prognosis of dnMBC between sexes imply similarities supporting the adoption of common treatment strategies.

12 1 - 50 of 76
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