Skip to main content
Erschienen in: Targeted Oncology 4/2018

14.06.2018 | Original Research Article

Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24)

verfasst von: Alberto Farolfi, Micaela Petrone, Emanuela Scarpi, Valentina Gallà, Filippo Greco, Claudia Casanova, Lucia Longo, Gennaro Cormio, Michele Orditura, Alessandra Bologna, Laura Zavallone, Jole Ventriglia, Elisena Franzese, Vera Loizzi, Donatella Giardina, Eva Pigozzi, Raffaella Cioffi, Sandro Pignata, Giorgio Giorda, Ugo De Giorgi

Erschienen in: Targeted Oncology | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking.

Objective

The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III–IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab.

Patients and Methods

Of the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms.

Results

In the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p < 0.0001). In multivariate analyses, the NLR was significantly associated with OS (p = 0.016), and the PLR was significantly associated with PFS (p = 0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p < 0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p = 0.026 and p = 0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p = 0.024 and p = 0.017, respectively).

Conclusion

Our results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.
Literatur
1.
2.
Zurück zum Zitat Karam A, Ledermann JA, Kim JW, et al. 5th ovarian Cancer consensus conference. In: Fifth Ovarian Cancer Consensus Conference of the gynecologic Cancer InterGroup: First-Line Interventions. Ann Oncol. 2017;28:711–7. Karam A, Ledermann JA, Kim JW, et al. 5th ovarian Cancer consensus conference. In: Fifth Ovarian Cancer Consensus Conference of the gynecologic Cancer InterGroup: First-Line Interventions. Ann Oncol. 2017;28:711–7.
3.
Zurück zum Zitat Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.CrossRefPubMed Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.CrossRefPubMed
4.
Zurück zum Zitat Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.CrossRefPubMed Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.CrossRefPubMed
5.
Zurück zum Zitat Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928–36.CrossRefPubMedPubMedCentral Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928–36.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Wilson MK, Pujade-Lauraine E, Aoki D, et al. Fifth ovarian Cancer consensus conference of the gynecologic Cancer InterGroup: recurrent disease. Ann Oncol. 2017;28:727–32.CrossRefPubMed Wilson MK, Pujade-Lauraine E, Aoki D, et al. Fifth ovarian Cancer consensus conference of the gynecologic Cancer InterGroup: recurrent disease. Ann Oncol. 2017;28:727–32.CrossRefPubMed
7.
Zurück zum Zitat Aghajanian C, Goff B, Nycum LR, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139:10–6.CrossRefPubMedPubMedCentral Aghajanian C, Goff B, Nycum LR, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139:10–6.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013;31:1219–1230. Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013;31:1219–1230.
12.
Zurück zum Zitat Templeton AJ, McNamara MG, Seruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:u124.CrossRef Templeton AJ, McNamara MG, Seruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:u124.CrossRef
13.
Zurück zum Zitat Santoni M, De Giorgi U, Iacovelli R, et al. Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013;109:1755–9.CrossRefPubMedPubMedCentral Santoni M, De Giorgi U, Iacovelli R, et al. Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013;109:1755–9.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Chua W, Charles KA, Baracos VE, Clarke SJ. Neutrophil/ lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011;104:1288–95.CrossRefPubMedPubMedCentral Chua W, Charles KA, Baracos VE, Clarke SJ. Neutrophil/ lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011;104:1288–95.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Rossi L, Santoni M, Crabb SJ, et al. High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial Cancer. Ann Surg Oncol. 2015;22:1377–84.CrossRefPubMed Rossi L, Santoni M, Crabb SJ, et al. High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial Cancer. Ann Surg Oncol. 2015;22:1377–84.CrossRefPubMed
16.
Zurück zum Zitat Conteduca V, Crabb SJ, Jones RJ, et al. Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer. PLoS One. 2016;11:e0158952.CrossRefPubMedPubMedCentral Conteduca V, Crabb SJ, Jones RJ, et al. Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer. PLoS One. 2016;11:e0158952.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Huang QT, Zhou L, Zeng WJ, et al. Prognostic significance of neutrophil-to-lymphocyte ratio in ovarian cancer: a systematic review and meta-analysis of observational studies. Cell Physiol Biochem. 2017;41:2411–8.CrossRefPubMed Huang QT, Zhou L, Zeng WJ, et al. Prognostic significance of neutrophil-to-lymphocyte ratio in ovarian cancer: a systematic review and meta-analysis of observational studies. Cell Physiol Biochem. 2017;41:2411–8.CrossRefPubMed
18.
Zurück zum Zitat Kwon HC, Kim SH, Oh SY, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17:216–22.CrossRefPubMed Kwon HC, Kim SH, Oh SY, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17:216–22.CrossRefPubMed
19.
Zurück zum Zitat Hu B, Yang XR, Xu Y, et al. Systemic immune- inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20:6212–22.CrossRefPubMed Hu B, Yang XR, Xu Y, et al. Systemic immune- inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20:6212–22.CrossRefPubMed
20.
Zurück zum Zitat Passardi A, Scarpi E, Cavanna L, et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget. 2016;7:33210–9.CrossRefPubMedPubMedCentral Passardi A, Scarpi E, Cavanna L, et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget. 2016;7:33210–9.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Lolli C, Caffo O, Scarpi E, et al. Systemic immune-inflammation index predicts the clinical outcome in patients with mcrpc treated with abiraterone. Front Pharmacol. 2016;7:376.CrossRefPubMedPubMedCentral Lolli C, Caffo O, Scarpi E, et al. Systemic immune-inflammation index predicts the clinical outcome in patients with mcrpc treated with abiraterone. Front Pharmacol. 2016;7:376.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Clarke S, Burge M, Cordwell C, et al. An australian translational study to evaluate the prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab (Avastin) [ASCENT]. BMC Cancer. 2013;13:120.CrossRefPubMedPubMedCentral Clarke S, Burge M, Cordwell C, et al. An australian translational study to evaluate the prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab (Avastin) [ASCENT]. BMC Cancer. 2013;13:120.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
24.
Zurück zum Zitat Moses K, Brandau S. Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells. Semin Immunol. 2016;28:187–96.CrossRefPubMed Moses K, Brandau S. Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells. Semin Immunol. 2016;28:187–96.CrossRefPubMed
25.
Zurück zum Zitat Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.CrossRefPubMed Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.CrossRefPubMed
26.
Zurück zum Zitat Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces epithelial-mesenchymal-like transition and promote metastasis. Cancer Cell. 2011;20:576–90.CrossRefPubMedPubMedCentral Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces epithelial-mesenchymal-like transition and promote metastasis. Cancer Cell. 2011;20:576–90.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13.CrossRefPubMed Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13.CrossRefPubMed
28.
Zurück zum Zitat Leffers N, Gooden MJ, de Jong RA, et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009;58:449–59.CrossRefPubMed Leffers N, Gooden MJ, de Jong RA, et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009;58:449–59.CrossRefPubMed
29.
Zurück zum Zitat Manning EA, Ullman JG, Leatherman JM, et al. A vascular endothelial growth factor receptor-2 inhibitor enhances antitumor immunity through an immune-based mechanism. Clin Cancer Res. 2007;13:3951–9.CrossRefPubMed Manning EA, Ullman JG, Leatherman JM, et al. A vascular endothelial growth factor receptor-2 inhibitor enhances antitumor immunity through an immune-based mechanism. Clin Cancer Res. 2007;13:3951–9.CrossRefPubMed
30.
Zurück zum Zitat Shrimali RK, Yu Z, Theoret MR, et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 2010;70:6171–80.CrossRefPubMedPubMedCentral Shrimali RK, Yu Z, Theoret MR, et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 2010;70:6171–80.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Kim HS, Choi HY, Lee M, et al. Systemic inflammatory response markers and CA-125 levels in ovarian clear cell carcinoma: a two center cohort study. Cancer Res Treat. 2016;48:250–8.CrossRefPubMed Kim HS, Choi HY, Lee M, et al. Systemic inflammatory response markers and CA-125 levels in ovarian clear cell carcinoma: a two center cohort study. Cancer Res Treat. 2016;48:250–8.CrossRefPubMed
34.
Zurück zum Zitat Grepin R, Guyot M, Jacquin M, et al. Acceleration of clear cell renal cell carcinoma growth in mice following bevacizumab/Avastin treatment: the role of CXCL cytokines. Oncogene. 2012;31:1683–94.CrossRefPubMed Grepin R, Guyot M, Jacquin M, et al. Acceleration of clear cell renal cell carcinoma growth in mice following bevacizumab/Avastin treatment: the role of CXCL cytokines. Oncogene. 2012;31:1683–94.CrossRefPubMed
35.
Zurück zum Zitat Stone RL, Nick AM, McNeish IA, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366:610–8. N Engl J Med. 2012;367:1768 (Erratum). Stone RL, Nick AM, McNeish IA, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366:610–8. N Engl J Med. 2012;367:1768 (Erratum).
36.
Zurück zum Zitat Middleton K, Jones J, Lwin Z, Coward JI. Interleukin-6: an angiogenic target in solid tumours. Crit Rev Oncol Hematol. 2014;89:129–39.CrossRefPubMed Middleton K, Jones J, Lwin Z, Coward JI. Interleukin-6: an angiogenic target in solid tumours. Crit Rev Oncol Hematol. 2014;89:129–39.CrossRefPubMed
Metadaten
Titel
Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24)
verfasst von
Alberto Farolfi
Micaela Petrone
Emanuela Scarpi
Valentina Gallà
Filippo Greco
Claudia Casanova
Lucia Longo
Gennaro Cormio
Michele Orditura
Alessandra Bologna
Laura Zavallone
Jole Ventriglia
Elisena Franzese
Vera Loizzi
Donatella Giardina
Eva Pigozzi
Raffaella Cioffi
Sandro Pignata
Giorgio Giorda
Ugo De Giorgi
Publikationsdatum
14.06.2018
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 4/2018
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0574-1

Weitere Artikel der Ausgabe 4/2018

Targeted Oncology 4/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.