Abstract

BackgroundBasal cell hyperplasia (BCH) and squamous metaplasia (SM) in the small bronchi distant from the tumor is associated with a high risk of non-small cell lung cancer (NSCLC) recurrence. Here, we assessed whether neoadjuvant chemotherapy (NAC), intraoperative radiotherapy (IORT), or adjuvant chemotherapy (AC) is effective to prevent recurrence in NSCLC patients (n=171) with different premalignant lesions in the small bronchiMethodsBCH, SM, and dysplasia (D) were identified in the samples of lung tissue distant from the tumor. NSCLC patients were treated by surgery, different combinations of NAC and IORT, and AC.ResultsBased on the type of bronchial lesions, NSCLC patients were classified into four groups: BCH+SM−D− (55.6%, 95/171), BCH+SM+D− (26.3%; 45/171), BCH−SM+D+ (6.4%, 11/171), and BCH−SM−D− (11.7%, 20/171). During 5 years, recurrent carcinoma was found in 13.4% (23/171) of patients and represented by metachronous metastases in the thoracic lymph nodes (82.6%, 19/23) and by a relapse in the bronchial stump (17.4%, 4/23). Recurrence was frequent in BCH+SM+D− patients (87.0%, 20/23), rare in BCH+SM−D− and BCH−SM−D− patients (13.0%, 3/23), and absent in BCH−SM+D+ patients (0/23). The 5-year recurrence-free survival was also shorter in BCH+SM+D− patients (HR 27.35; 95% CI: 6.31−118.48; P<0.0001). In the high-risk (BCH+SM+D−) group, recurrence occurred mainly in cases without NAC and IORT (88.2%, 15/17) and was absent (0/15) when these therapies were combined. NAC- and IORT-negative patients also showed poor overall survival (HR 4.35; 95% CI: 1.96−9.66; P<0.0001) and tended to have decreased recurrence-free survival (P=0.075). Importantly, the recurrence rate was not different between AC-treated and AC-naïve BCH+SM+D− patients.ConclusionsThe combination of NAC and IORT is an effective strategy to prevent recurrence in high-risk NSCLC patients.

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