Development and Validation of a Simplified Prognostic Score in SCLC

Elodie Negre, Amandine Coffy, Alexandra Langlais, Jean-Pierre Daures, Armelle Lavole, Elisabeth Quoix, Olivier Molinier, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Virginie Westeel, Franck Morin, Benoît Roch, Jean-Louis Pujol, Elodie Negre, Amandine Coffy, Alexandra Langlais, Jean-Pierre Daures, Armelle Lavole, Elisabeth Quoix, Olivier Molinier, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Virginie Westeel, Franck Morin, Benoît Roch, Jean-Louis Pujol

Abstract

Introduction: This study aimed at generating a new simplified prognostic score (SPS) using common clinical and biological variables to discriminate a limited number of subgroups of patients with SCLC differing by their overall survival (OS).

Methods: The SPS was developed exploring the Montpellier University Hospital retrospective database of 401 patients over a 16-year period. All patients had received etoposide - platinum-based chemotherapy as first-line treatment. The SPS development took into account significant determinants of OS in the Cox model, weighted by their regression β coefficients. Validation of the consequent SPS has been done separately in a combined population of 213 patients accrued from two different published trials (NCT03059667 and NCT00930891).

Results: The significant independent determinants of OS included the following: (1) American Joint Committee on Cancer TNM stage IV (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 1.91-3.33); (2) Eastern Cooperative Oncology Group performance status greater than 1 (HR: 2.27; 95% CI: 1.79-2.87); (3) the presence of liver metastases (HR: 1.66; 95% CI: 1.29-2.15); and (4) neutrophil-to-lymphocyte ratio greater than 4 (HR: 1.39; 95% CI: 1.11-1.92). The SPS generated with these four variables, segregated three groups (good, intermediate, and poor prognosis) with respective median OS of 26.9 months (95% CI: 20.1-38.9), 11.5 months (95% CI: 9.8-13.0), and 6.8 months (95% CI: 5.8-8.3; log-rank p < 10-4). Harrell's C statistic estimate was 0.68 ± 0.012, suggesting goodness of calibration. In the validation cohort, the SPS segregated the aforementioned three subgroups in a nearly similar manner, with respective median OS: 27.2, 12.3, and 8.6 months (log-rank p < 10-3; Harrell's C statistic: 0.58 ± 0.02).

Conclusions: The SPS is easy to calculate in real-life practice and efficiently discriminates three populations with different prognoses. This study deserves further validation of this score in patients with SCLC receiving immunochemotherapy.

Keywords: Chemotherapy; Prognosis; Prognostic score; Serum markers; Small cell lung cancer.

© 2020 The Authors.

Figures

Figure 1
Figure 1
Kaplan-Meier estimate of overall survival according to patients’ subgroups defined by the primary score in the development cohort (log-rank: p < 0.01)
Figure 2
Figure 2
Kaplan-Meier estimate of overall survival according to patients’ subgroups defined by the simplified prognostic score in the development cohort: group I: good prognosis (score 0 or 0.5); group II: intermediate prognosis (scores 1, 1.5, or 2); group III: poor prognosis (score 2.5 or 3). (A) Development cohort (log-rank: p < 0.01); (B) validation cohort (log-rank: p < 10-4).
Figure 3
Figure 3
Kaplan-Meier estimate of progression-free survival according to patients’ subgroups defined by the simplified prognostic score in the development cohort: group I: good prognosis (score 0 or 0.5); group II: intermediate prognosis (scores 1, 1.5, or 2); group III: poor prognosis (score 2.5 or 3).

References

    1. Arriagada R., Le Chevalier T., Pignon J.P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993;329:1848–1852.
    1. Pujol J.L., Breton J.L., Gervais R. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007;25:3945–3951.
    1. Spigel D.R., Townley P.M., Waterhouse D.M. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29:2215–2222.
    1. Ready N.E., Pang H.H., Gu L. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: a randomized, double-blind, placebo-controlled Phase II study-CALGB 30504 (alliance) J Clin Oncol. 2015;33:1660–1665.
    1. Morgensztern D., Besse B., Greillier L. Efficacy and safety of rovalpituzumab tesirine in third-line and beyond patients with DLL3-expressing, relapsed/refractory small-cell lung cancer: results from the phase II TRINITY study. Clin Cancer Res. 2019;25:6958–6966.
    1. de Bono J., Ramanathan R.K., Mina L. Phase I, dose-escalation, two-part trial of the PARP inhibitor talazoparib in patients with advanced germline BRCA1/2 mutations and selected sporadic cancers. Cancer Discov. 2017;7:620–629.
    1. Gardner E.E., Lok B.H., Schneeberger V.E. Chemosensitive relapse in small cell lung cancer proceeds through an EZH2-SLFN11 axis. Cancer Cell. 2017;31:286–299.
    1. Owonikoko T.K., Niu H., Nackaerts K. Randomized phase II study of paclitaxel plus alisertib versus paclitaxel plus placebo as second-line therapy for SCLC: primary and correlative biomarker analyses. J Thorac Oncol. 2020;15:274–287.
    1. Kalemkerian G.P., Loo B.W., Akerley W. NCCN guidelines insights: small cell lung cancer, version 2.2018. J Natl Compr Cancer Netw. 2018;16:1171–1182.
    1. Paz-Ares L., Dvorkin M., Chen Y. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (Caspian): a randomised, controlled, open-label, phase 3 trial. Lancet Lond Engl. 2019;394:1929–1939.
    1. Horn L., Mansfield A.S., Szczęsna A. First-line Atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–2229.
    1. Micke P., Faldum A., Metz T. Staging small cell lung cancer: veterans administration lung study group versus international association for the study of lung cancer—what limits limited disease? Lung Cancer. 2002;37:271–276.
    1. Nicholson A.G., Chansky K., Crowley J. The international association for the study of lung cancer lung cancer staging project: proposals for the revision of the clinical and pathologic staging of small cell lung cancer in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:300–311.
    1. Cerny T., Anderson H., Bramwell V., Thatcher N., Blair V. Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients. Int J Cancer. 1987;39:146–149.
    1. Wang S., Yang L., Ci B. Development and validation of a nomogram prognostic model for SCLC patients. J Thorac Oncol. 2018;13:1338–1348.
    1. Deyo R.A., Cherkin D.C., Ciol M.A. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613–619.
    1. Zhou T., Hong S., Hu Z. A systemic inflammation-based prognostic scores (mGPS) predicts overall survival of patients with small-cell lung cancer. Tumor Biol. 2015;36:337–343.
    1. Pujol J.L., Lavole A., Quoix E. Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†. Ann Oncol. 2015;26:908–914.
    1. Pujol J.L., Greillier L., Audigier-Valette C. A randomized non-comparative phase II study of anti-programmed cell death-ligand 1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 trial. J Thorac Oncol. 2019;14:903–913.
    1. Maestu I., Pastor M., Gómez-Codina J. Pretreatment prognostic factors for survival in small-cell lung cancer: a new prognostic index and validation of three known prognostic indices on 341 patients. Ann Oncol. 1997;8:547–553.
    1. Xie D., Marks R., Zhang M. Nomograms predict overall survival for patients with small-cell lung cancer incorporating pretreatment peripheral blood markers. J Thorac Oncol. 2015;10:1213–1220.
    1. Brink I., Schumacher T., Mix M. Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2004;31:1614–1620.
    1. Ren Y., Dai C., Zheng H. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis. Oncotarget. 2016;7:53245–53253.
    1. Li J., Zhu H., Sun L., Xu W., Wang X. Prognostic value of site-specific metastases in lung cancer: a population based study. J Cancer. 2019;10:3079–3086.
    1. Tumeh P.C., Hellmann M.D., Hamid O. Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res. 2017;5:417–424.
    1. Fridlender Z.G., Sun J., Kim S. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;8:183–194.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit