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)

Pierpaolo Pastina, Valerio Nardone, Cirino Botta, Stefania Croci, Paolo Tini, Giuseppe Battaglia, Veronica Ricci, Maria Grazia Cusi, Claudia Gandolfo, Gabriella Misso, Silvia Zappavigna, Michele Caraglia, Antonio Giordano, Donatella Aldinucci, Pierfrancesco Tassone, Pierosandro Tagliaferri, Luigi Pirtoli, Pierpaolo Correale

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)75904-75913
Number of pages10
JournalOncotarget
Volume8
Issue number44
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Etoposide
Cisplatin
Lung Neoplasms
Radiotherapy
Survival
Drug Therapy
Neoplasms
Aptitude
Therapeutics
Non-Small Cell Lung Carcinoma
Dendritic Cells
Disease-Free Survival
Neoplasm Metastasis
T-Lymphocytes
Safety
Bevacizumab

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 journalArticle

Pastina, P, Nardone, V, Botta, C, Croci, S, Tini, P, Battaglia, G, Ricci, V, Cusi, MG, Gandolfo, C, Misso, G, Zappavigna, S, Caraglia, M, Giordano, A, Aldinucci, D, Tassone, P, Tagliaferri, P, Pirtoli, L & Correale, P 2017, '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)', Oncotarget, vol. 8, no. 44, pp. 75904-75913. https://doi.org/10.18632/oncotarget.20411
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. / 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). In: Oncotarget. 2017 ; Vol. 8, No. 44. pp. 75904-75913.
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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

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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].

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