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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Predictive and Prognostic Clinical Variables in Cancer Patients Treated With Adenoviral Oncolytic Immunotherapy
Kristian Taipale1, Ilkka Liikanen1, Anniina Koski1
1Cancer Gene Therapy Group, University of Helsinki, Faculty of Medicine, Helsinki, Finland.
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.
Insights
Oncolytic adenovirus immunotherapy shows promise, with factors like no liver metastases and female sex improving outcomes. Low neutrophil-to-lymphocyte ratio predicts longer survival in cancer patients.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic viruses are advancing in cancer therapy.
- Clinical data analysis is essential for improving virotherapy treatments.
Purpose of the Study:
- To analyze clinical data from 290 patients treated with oncolytic adenovirus.
- To identify factors influencing treatment response and overall survival (OS).
- To investigate the impact of neutralizing antibodies, tumor burden, and leukocyte counts.
Main Methods:
- Statistical modeling of clinical variables and treatment characteristics.
- Multivariate analysis to assess prognostic factors.
- Evaluation of imaging response and overall survival.
Main Results:
- Absence of liver metastases correlated with better disease control (P = 0.021).
- Viruses coding for granulocyte macrophage colony-stimulating factor (GM-CSF) and female sex were linked to better prognosis (HR 0.378, P < 0.001; HR 0.694, P = 0.017).
- Intraperitoneal injection improved disease control (OR 3.246, P = 0.027), and low neutrophil-to-lymphocyte ratio predicted longer OS (P < 0.001).
Conclusions:
- Clinical factors like metastasis absence, GM-CSF encoding viruses, and intraperitoneal delivery impact oncolytic adenovirus efficacy.
- Neutrophil-to-lymphocyte ratio is a significant predictor of overall survival.
- Findings support treatment optimization and patient selection for oncolytic adenovirus immunotherapy.
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