title: Predictive and Prognostic Clinical Variables in Cancer Patients Treated With Adenoviral Oncolytic Immunotherapy.
abstract: The development of oncolytic viruses has recently made great progress towards being available to cancer patients. With the breakthrough into clinics, it is crucial to analyze the existing clinical experience and use it as a basis for treatment improvements. Here, we report clinical data from 290 patients treated with oncolytic adenovirus. Using clinical variables and treatment characteristics, we constructed statistical models with regard to treatment response and overall survival (OS). Additionally, we investigated effects of neutralizing antibodies, tumor burden, and peripheral blood leucocyte counts on these outcomes. We found the absence of liver metastases to correlate with an improved rate of disease control (P = 0.021). In multivariate evaluation, patients treated with viruses coding for immunostimulatory granulocyte macrophage colony-stimulating factor were linked to better prognosis (hazard ratio (HR) 0.378, P < 0.001), as well as women with any cancer type (HR 0.694, P = 0.017). In multivariate analysis for imaging response, patients treated via intraperitoneal injection were more likely to achieve disease control (odds ratio (OR) 3.246, P = 0.027). Patients with low neutrophil-to-lymphocyte ratio before treatment had significantly longer OS (P < 0.001). These findings could explain some of the variation seen in treatment outcomes after virotherapy. Furthermore, the results offer hypotheses for treatment optimization and patient selection in oncolytic adenovirus immunotherapy.
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Kristian
authors.initials: K
authors.lastname: Taipale
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Liikanen
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Koski
authors.affiliation: Targovax ASA, Helsinki, Finland.
authors.forename: Raita
authors.initials: R
authors.lastname: Heiskanen
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.|Department of Obstetrics and Gynecology, HUCH, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Otto
authors.initials: O
authors.lastname: Hemminki
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Grönberg-Vähä-Koskela
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Docrates Cancer Center, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.affiliation: Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.|Helsinki University Hospital Comprehensive Cancer Center, Finland.|TILT Biotherapeutics Ltd., Helsinki, Finland.
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007958:Leukocyte Count; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D016017:Odds Ratio; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D014057:Tomography, X-Ray Computed; D019076:Transgenes; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor