Prognostic Impact of Thyroid Transcription Factor-1 Expression and the Efficacy of Carboplatin Plus (Nab-) Paclitaxel in Non-Squamous Non-Small Cell Lung Cancer Complicated with Idiopathic Interstitial Pneumonias.

Background:Previous studies have reported an association between expression of thyroid transcription factor 1 (TTF-1) and the efficacy of immune checkpoint inhibitors (ICIs), cytotoxic chemotherapy, and immunochemotherapy in patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of cytotoxic chemotherapy in patients with NS-NSCLC with idiopathic interstitial pneumonias (IIPs) remains unclear. This study aimed to evaluate the relationship TTF-1 expression and the efficacy of platinum-doublet chemotherapy in patients with NS-NSCLC with coexisting IIPs. Methods:This retrospective study reviewed 120 patients with NSCLC complicated by IIPs who were treated at Nippon Medical School Hospital in Japan between January 2010 and December 2024. We analyzed the efficacy and safety of carboplatin and either paclitaxel or nanoparticle albumin-bound (nab-) paclitaxel for NS-NSCLC with IIPs. Results:In the total cohort, 51 patients were evaluated for TTF-1 expression status and administered carboplatin plus (nab-) paclitaxel as first-line therapy. TTF-1 expression was observed in 32 patients (63%). Twenty-five patients (49%) exhibited a usual interstitial pneumonia (UIP) pattern. The overall response rate (ORR) was significantly higher in the TTF-1-positive group compared to the TTF-1-negative group (62.4% vs. 31.6%, P=0.045). Median overall survival (OS) and progression-free survival (PFS) were also significantly longer in the TTF-1-positive group than in TTF-1-negative group (11.3 vs. 8.2 months, P=0.007; 8.4 vs. 4.4 months, P<0.001). TTF-1 negativity was identified as an independent prognostic factor associated with inferior OS and PFS in multivariate analysis. Furthermore, the TTF-1-negative group had a significantly higher incidence of lung cancer development in the setting of underlying interstitial pneumonia (IP) (P<0.001), suggesting that decreased TTF-1 expression may be involved in the pathogenesis of lung cancer arising from IIPs. Conclusions:TTF-1 expression is an independent prognostic factor in patients with NS-NSCLC complicated by IIPs who received carboplatin plus (nab-) paclitaxel. TTF-1 expression may represent a valuable biomarker for characterizing the disease subtypes and guiding therapeutic strategies in lung cancer with coexisting IIPs.