Tumor Purity as a Prognostic and Predictive Biomarker of Postoperative Radiation Therapy Outcomes in Stage IIIA-N2 Non-Small Cell Lung Cancer: A Transcriptomic Analysis From the Lung ART Trial
Abstract
Purpose: Tumor purity (TP), the proportion of malignant cells within a tumor sample, is an important feature of the tumor microenvironment. Using transcriptomic data from the Lung ART-IFCT 0503 trial, we investigated the relevance of TP and its potential to predict benefit from postoperative radiation therapy (PORT).
Methods and materials: RNA sequencing was successfully performed on 285 samples. TP was inferred using the ESTIMATE algorithm. Associations with overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier and multivariable Cox models.
Results: Among 285 patients with resected stage IIIA-N2 non-small cell lung cancer, 144 received PORT. The median age was 61 years, 31% were women, and 80% had nonsquamous histology. Baseline characteristics were well balanced between arms. The median TP was 0.64 (range, 0.41-0.92) and was slightly higher in the PORT arm (0.65 vs 0.63; P = .006). TP correlated with H&E pathologist-estimated cellularity (r = 0.23, P -6). Transcriptomic analysis confirmed associations with proliferation-related pathways and reduced hypoxia signatures (false discovery rate < 0.001). TP inversely correlated with T-cell immune infiltration by immunohistochemistry (CD3⁺ r = -0.52; CD8⁺ r = -0.45). High-TP was associated with worse OS (48.5 vs 106.5 months, P < .001) and DFS (18.4 vs 48.0 months, P = .017). A TP × PORT interaction was observed for OS (P = .049) and a trend for DFS (P = .07).
Conclusions: TP reflects…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 285 participants or records.
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