Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery

Sarit Appel*, Jair Bar*, Akram Saad, Edith Michelle Marom, Damien Urban, Amir Onn, Hadas Gantz-Sorotsky, Ran Yosef Kremer, Alon Ben-Nun, Marina Perelman, Efrat Ofek, Rinat Yacobi, Sameh Daher, Adi Rasco, Zvi Symon, Yaacov Richard Lawrence, Jeffrey Goldstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC). Methods Patients with Stage IIB-IIIA NSCLC treated with NA-ChRT, completion surgery, and underwent molecular profile testing were identified in a lung cancer data-base. Pathologic response was quantified using: (i) major pathologic response (MPR), (ii) complete pathologic response (pCR), and (iii) mean residual viable tumor cells (MRTC). Two groups were formed based on the presence or absence of driver mutations. Clinical and pathological correlations between the groups were studied. Results Forty-seven patients underwent tumor molecular profile testing, NA-ChRT, and completion surgery. Compared to the no-driver mutation group, the driver mutation group had lower MPR (23% vs 71%, p = 0.003), pCR (0% vs 26%, p = 0.02), and higher MRTC (43.4% vs 15.8%, p = 0.009). Univariate analysis showed an increased MPR rate for smokers, squamous cell histology, ChRT-surgery interval >65 days, and no-driver mutations. Multivariate analysis showed that only no-driver mutations (OR 0.39, p = 0.02) remained significant for MPR. PD-L1 status did not affect MPR. At 2 years, the driver mutation group had lower rates of local control (Hazard ration [HR] 0.67, p = 0.17) and disease-free survival (HR 0.5, p = 0.001). Overall survival was similar for both groups (HR = 1.04, p = 0.86). Conclusion Following 60 Gray NA-ChRT, tumors with a driver mutation had lower MPR and pCR rates than tumors without a driver mutation. PD-L1 was not associated with tumor regression. Advances in knowledge Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

Original languageEnglish
Article number20220763
JournalBritish Journal of Radiology
Volume96
Issue number1152
DOIs
StatePublished - 1 Nov 2023

Fingerprint

Dive into the research topics of 'Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery'. Together they form a unique fingerprint.

Cite this