18. NY-ESO-1 as a predictive marker for neoadjuvant chemotherapy in stage 3a non- small-cell lung cancer (NSCLC)

Abstract

Background The use of neoadjuvant chemotherapy in Stage 3A NSCLC is controversial with trials consistently failing to demonstrate significant benefit. The ability to predict tumour chemor-esponsiveness should aid clinical trial design and outcome. Can-cer-Testis antigens (CTAg), such as MAGE-A3, are currently being investigated as immunotherapeutic targets in the adjuvant setting. CTAgs are expressed in over 50% of both squamous cell and adenocarcinomas but restricted to testis in normal tissues. Since CTAgs have been proposed as markers of drug-resistant stem-like cells, we investigated their expression and association with chemosensitivity. Methods Stage 3A patients treated with neoadjuvant chemotherapy at the Austin Hospital (AH) Melbourne and Weill Cornell Medical College (WCMC) NY were investigated. Preoperative mediastinal lymphadenectomy tissues were stained for a panel of CTAgs including NY-ESO-1, MAGE-A, MAGE-C1, GAGE and CT45 by immunohistochemistry. Results were correlated to clinical characteristics, chemoresponsiveness (defined as pathological down-staging of TNM status), progression-free and overall survival (OS). Results 95 patients (WCMC 70, AH 25) were studied. Staining for one or more CTAgs was positive in 50% of samples regardless of histology. NY-ESO-1 was expressed in 33% of samples. NY-ESO-1 expression was significantly associated with chemosensitivity in both datasets (Chi square, p = 0.010). Improved OS was only seen in the AH dataset (HR 0.36; 95%CI 0.14–0.96, p = 0.04). Conclusions Expression of NY-ESO-1 predicts response to neoadjuvant chemotherapy in stage 3A NSCLC. Expression occurred in both adenocarcinoma and squamous cell carcinoma. Given their immunogenicity, immunological mechanisms for these responses are being investigated.