Abstract
Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs > 1: 4+/-5.389 (95%CI,0-14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory-T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤1 vs > 1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045].
| Original language | English |
|---|---|
| Pages (from-to) | 75904-75913 |
| Number of pages | 10 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 44 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- Immune-modulation
- Metronomic chemotherapy
- NSCLC
- Radiation therapy
- Retrospective analysis
ASJC Scopus subject areas
- Oncology
Cite this
Radiotherapy prolongs the survival of advanced non-smallcell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev). / Pastina, Pierpaolo; Nardone, Valerio; Botta, Cirino; Croci, Stefania; Tini, Paolo; Battaglia, Giuseppe; Ricci, Veronica; Cusi, Maria Grazia; Gandolfo, Claudia; Misso, Gabriella; Zappavigna, Silvia; Caraglia, Michele; Giordano, Antonio; Aldinucci, Donatella; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Pirtoli, Luigi; Correale, Pierpaolo.
In: Oncotarget, Vol. 8, No. 44, 01.01.2017, p. 75904-75913.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Radiotherapy prolongs the survival of advanced non-smallcell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)
AU - Pastina, Pierpaolo
AU - Nardone, Valerio
AU - Botta, Cirino
AU - Croci, Stefania
AU - Tini, Paolo
AU - Battaglia, Giuseppe
AU - Ricci, Veronica
AU - Cusi, Maria Grazia
AU - Gandolfo, Claudia
AU - Misso, Gabriella
AU - Zappavigna, Silvia
AU - Caraglia, Michele
AU - Giordano, Antonio
AU - Aldinucci, Donatella
AU - Tassone, Pierfrancesco
AU - Tagliaferri, Pierosandro
AU - Pirtoli, Luigi
AU - Correale, Pierpaolo
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs > 1: 4+/-5.389 (95%CI,0-14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory-T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤1 vs > 1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045].
AB - Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs > 1: 4+/-5.389 (95%CI,0-14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory-T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤1 vs > 1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045].
KW - Immune-modulation
KW - Metronomic chemotherapy
KW - NSCLC
KW - Radiation therapy
KW - Retrospective analysis
UR - http://www.scopus.com/inward/record.url?scp=85030308433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030308433&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.20411
DO - 10.18632/oncotarget.20411
M3 - Article
VL - 8
SP - 75904
EP - 75913
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 44
ER -