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Predictive and prognostic clinical variables in cancer patients treated with adenoviral oncolytic immunotherapy

Taipale, K; Liikanen, I; Koski, A; Heiskanen, R; Kanerva, A; Hemminki, O; Oksanen, M; Grönberg-Vähä-Koskela, S; Hemminki, K LU and Joensuu, T, et al. (2016) In Molecular Therapy
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. 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... (More)

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. 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 (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 (OR 3.246, p=0.027). Patients with low neutrophil-to-lymphocyte ratio before treatment, had significantly longer overall survival (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.Molecular Therapy (2016); doi:10.1038/mt.2016.67.

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Molecular Therapy
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Nature Publishing Group
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  • Scopus:84965010332
ISSN
1525-0024
DOI
10.1038/mt.2016.67
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English
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yes
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ed877298-9bcf-44ae-961a-e40f9c499cd2
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2016-04-28 11:10:56
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2016-10-28 12:12:49
@misc{ed877298-9bcf-44ae-961a-e40f9c499cd2,
  abstract     = {<p>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. 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 (HR 0.378, p&lt;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 (OR 3.246, p=0.027). Patients with low neutrophil-to-lymphocyte ratio before treatment, had significantly longer overall survival (p&lt;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.Molecular Therapy (2016); doi:10.1038/mt.2016.67.</p>},
  author       = {Taipale, K and Liikanen, I and Koski, A and Heiskanen, R and Kanerva, A and Hemminki, O and Oksanen, M and Grönberg-Vähä-Koskela, S and Hemminki, K and Joensuu, T and Hemminki, A},
  issn         = {1525-0024},
  language     = {eng},
  month        = {04},
  publisher    = {ARRAY(0xaeecc80)},
  series       = {Molecular Therapy},
  title        = {Predictive and prognostic clinical variables in cancer patients treated with adenoviral oncolytic immunotherapy},
  url          = {http://dx.doi.org/10.1038/mt.2016.67},
  year         = {2016},
}