Transcriptomics in tumor and normal lung tissues identify early-stage NSCLC patients with high risk of post-surgery recurrence who may benefit from adjuvant therapies

Posted: Friday, September 16, 2022

September 15, 2022
JCO® Precision Oncology

PURPOSE The prognosis of patients with non–small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective
adjuvant treatments can be offered to those at highest risk of recurrence.

METHODS Relative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery.

RESULTS Low versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in
patients with TNM stages 1-2 (P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS (P = .0041). High co-overexpression of CTLA-4, PD-
L1, and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS (P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (P = 2.12E–11).

CONCLUSION TNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC.

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AUTHORS
Vladimir Lazar, MD, PhD; Nicolas Girard, MD, PhD; Eric Raymond, MD, PhD; Jean-François Martini, PhD; Susan Galbraith, PhD;
Jacques Raynaud, MBA; Catherine Bresson, MBA; Benjamin Solomon, MD, PhD; Shai Magidi, MS; Hovav Nechushtan, MD;
Amir Onn, MD, PhD; Raanan Berger, MD, PhD; Haiquan Chen, MD, PhD; Amal Al-Omari, PhD; Sadakatsu Ikeda, MD, PhD; Ulrik Lassen, MD; Marina Sekacheva, PhD; Enriqueta Felip, MD; Josep Tabernero, MD, PhD; Gerald Batist, MD, PhD; Alan Spatz, MD, PhD; C.S. Pramesh, MD, PhD; Philippe Girard, MD; Jean-Yves Blay, MD, PhD; Thierry Philip, MD, PhD; Ioana Berindan-Neagoe, PhD; Angel Porgador, PhD; Eitan Rubin, PhD; Razelle Kurzrock, MD, PhD; and Richard L. Schilsky, MD