Abstract 2165: Reproducibility of a 12-gene panel and development of user-friendly nomogram-based calculator for clinical management of surgically resected non-small cell lung cancer patients
Authors: Leal Leticia Ferro , Gonçalves Maria Fernanda Santiago , da Silva Luciane Sussuchi , Lima Marcos Alves , Olveira Marco , Yin Shen , Bastos Helder Novais e , De Marchi Pedro , Dias Josiane Mourao , Carneiro Fatima , Moura Conceição Souto , da Silva Vinicius Duval , Witsuba Ignacio I. , Yang Xie , Reis Rui M. 
Published: July 2021

Introduction: Most NSCLC patients treated with curative approaches will experience relapses and disease progression regardless of adjuvant chemotherapy (ACT). Currently, specific criteria lack to define patients who will be benefited from ACT.

Aim: To validate a 12-gene panel for predicting outcome and ACT benefit in NSCLC patients and to build a user-friendly nomogram-based calculator for estimation of survival probability.

Methods: Surgically resected NSCLC patients were retrospectively selected (n=118) and tumor tissues (FFPE) were used for RNA isolation (RNeasy FFPE Mini Kit). The 12-gene panel (ATP8A1, AURKA, C1orf116, COL4A3, DOCK9, HOPX, HSD17B6, IFT57, MBIP, NKX2-1, RRM2, TTC37) was evaluated by ElementsXT (NanoString) and normalized by housekeeping genes - developed by Yang et al, 2019. The risk score was calculated (PCA-based model) and a cutoff value was set (R mclust package) to stratify patients into two groups: high-risk patients (n=59; ACT benefit) and low-risk patients (n=59; ACT non-benefit). Kaplan-Meier and Log-rank test were used for survival analysis and for evaluating prognostic performance of the 12-gene panel (all patients with no event were censored at 60 months of follow up for both overall - OS - and progression-free survival - PFS). Cox Regression model was used for the development of the nomogram model and significant variables were employed for the final model and for the user-friendly nomogram-based calculator.

Results: The 12-gene panel stratified the patients (n=118) into two groups, high-risk and low-risk groups for both OS and PFS (HR=4.21; p&lt;0.0001 and HR=5.23; p&lt;0.0001, respectively), regardless of ACT treatment. The low-risk group - stratified into ACT-treated (n=20) and ACT-untreated (n=39) patients - exhibit higher OS for ACT-untreated patients (HR=3.88; p=0.046). The high-risk group - stratified into ACT-treated (n=27) and ACT-untreated (n=32) patients - exhibit similar OS for ACT-treated and ACT-untreated patients (p=0.131 and p=0.134, respectively). High-risk group presented worse outcome for OS (p=0.001; HR=3.57) and PFS (p=&lt;0.0001; HR=4.81) and stage IIIA patients also presented worse outcome for OS (p=0.002; HR=3.69) and PFS (p=0.0004; HR=3.38).The nomogram was built with risk score (Low-risk; High-risk) and disease stage at diagnosis (IA/IB/IIA, IIB, IIIA) - maximum points OS=200; maximum points PFS=180 - and the user-friendly calculator was set up accordingly to determine OS and PFS probability in 1-, 3- and 5-year.

Conclusion: The 12-gene panel successfully stratified resected NSCLC patients into high- and low-risk groups. The nomogram-based calculator combining clinical features and molecular results may be an useful and user-friendly tool for oncologists to better guide treatment strategies with curative intent for NSCLC patients.

Citation Format: Leticia Ferro Leal, Maria Fernanda Santiago Gonçalves, Luciane Sussuchi da Silva, Marcos Alves Lima, Marco Olveira, Shen Yin, Helder Novais e Bastos, Pedro De Marchi, Josiane Mourao Dias, Fatima Carneiro, Conceição Souto Moura, Vinicius Duval da Silva, Ignacio I. Witsuba, Xie Yang, Rui M. Reis. Reproducibility of a 12-gene panel and development of user-friendly nomogram-based calculator for clinical management of surgically resected non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2165.