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LACE-Bio：新肺腺癌分类在辅助化疗研究中的预后和预测价值
O17.01 | Prognostic and predictive value of a new IASLC/ATS/ERS lung adenocarcinoma classification in a pooled analysis of four adjuvant chemotherapy trials: a LACE-Bio study Authors: Elisabeth M. Brambilla1, Sophie Marguet2, Gwénaël Le Teuff2, Sylvie Lantuejoul1, Frances A. Shepherd3, Lesley Seymour4, Robert Kratzke5, Stephen L. Graziano6, Hans Popper7, Jean-Pierre Pignon2, Rafael Rosell8, Jean-Yves Douillard9, Thierry Le Chevalier2, Jean-Charles Soria2, Ming-Sound Tsao10
1Institut Albert Bonniot, Grenoble/FRANCE, 2Gustave Roussy, Villejuif/FRANCE, 3Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON/CANADA, 4Queen's University, Kingston, ON/CANADA, 5University of Minnesota, Minneapolis, MN/UNITED STATES OF AMERICA, 6SUNY Upstate Medical University, Syracuse, NY/UNITED STATES OF AMERICA, 7University Medical School of Graz, Graz/AUSTRIA, 8Catalan Institute of Oncology, Barcelona/SPAIN, 9ICO R Gauducheau, St Herblain/FRANCE, 10University Health Network, University of Toronto, Toronto, ON/CANADA Background A new IASLC/ATS/ERS classification for lung adenocarcinoma has been proposed to classify invasive lung adenocarcinoma patients according to the predominant growth pattern present in the tumor: lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MPP) and solid (SOL). Several studies have reported consistently that early stage resectable lung adenocarcinoma patients with LEP predominant pattern have a better prognosis, while MPP and SOL predominant patterns have a significantly poorer prognosis. However, the prognostic significance of these histological patterns has not been tested in clinical trials. Furthermore, the clinical utility of this new classification for predicting benefit from adjuvant chemotherapy is unknown. Methods The representative single H&E slide of 1766 non-small cell lung cancer patients from IALT, JBR.10, CALGB 9633 and ANITA adjuvant chemotherapy trials who participated in the LACE-Bio study were reviewed to confirm the histological diagnosis. These cases were independently assessed by two pathologists involved in the development of this new IASLC/ATS/ERS classification for subtyping. Discordant cases were resolved by consensus. Clinical outcomes were overall survival (OS, main outcome), disease-free survival (DFS) and specific disease-free survival (SDFS) (DFS with censoring deaths not related to cancer). Multivariable Cox models stratified by trial were used for prognostic analyses and the interaction between treatment (chemotherapy / control) and histology subtypes added for predictive analyses. The five histology subtypes were first analysed separately and 3 groups (LEP, PAP+ACN and MPP+SOL) were considered. Results 573 patients were classified as 23 (4%) as LEP, 148 (26%) as ACN, 99 (17%) as PAP, 39 (7%) as MPP and 264 (46%) as SOL. The distribution of histology subtypes was different across trials (p=0.02) but not related with standard prognostic variables. The number of deaths, events and cancer-related events were 269, 320 and 292 respectively. No significant difference was observed between the survival curves of 5 subtypes whatever the endpoint. No prognostic value of 3 histological subtypes was observed for OS (p=0.21 in the control arm) contrary to DFS (p=0.04) and SDFS (p=0.03). These last 2 results were explained by the difference between PAP+ACN and MPP+SOL with hazard ratio (HR)ACN+PAP vs. MPP+SOL=0.66 95% confidence interval (CI)=[0.47-0.91] and HRACN+PAP vs. MPP+SOL=0.67 [0.44-0.89] for DFS and SDFS, respectively. Due to the small number of patients with LEP predominant pattern, the predictive value was assessed after excluding this subtype. MPP+SOL patients reported significant DFS benefit from adjuvant chemotherapy (HR=0.58 [0.43-0.80], p<0.001) compared to ACN+PAP patients (HR=1.12 [0.79-1.59], p=0.53; p interaction < 0.01). A similar result was observed for SDFS with HR=0.58 [0.42-0.80], p<0.005 in MPP+SOL compared to HR=1.13 [0.78-1.63], p=0.52 in ACN+PAP (p interaction <0.01) while no predictive effect for OS. Conclusion Resectable lung adenocarcinoma patients with micropapillary and solid predominant patterns showed a trend for poorer DFS and SDFS compared to patients with the other subtypes, and they show a significantly higher benefit from adjuvant chemotherapy on these outcomes. Histological subtypes according to the IASLC/ATS/ERS classification may be proposed as a stratification factor in design of future adjuvant chemotherapy trials.
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