Neoadjuvant therapy can improve outcome by increasing the resection rate, down staging the primary tumor and improving postoperative survival. PD-1/PD-L1 inhibitors have been approved in the treatment of advanced lung cancer, breast cancer, melanoma and other common cancers, and its success has moved immunotherapy forward to the early stage setting. In this study, we summarized the ongoing clinical trials which focus on neoadjuvant immunotherapy in solid cancers, and discussed their treatment strategy, efficacy and adverse events.

Introduction:In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALKpositive NSCLC, brigatinib exhibited superior progressionfree survival (PFS) versus crizotinib in the two planned interim analyses.Here, we report the final efficacy, safety, and exploratory results.

Tumor suppressor genes TSC1 and TSC2 inhibit cell growth through inactivation the function of mTORC1. Previous studies have demonstrated that loss of function mutation of either TSC1 or TSC2 gene result in formation of neoplasm in multiple tissues. However, the clinical significance of TSC1 and TSC2 in non-small-cell lung cancer (NSCLC) remains unknown. This study aimed to investigate the clinical and molecular characteristics of TSC1 and TSC2 mutation in NSCLC patients.

Patient-derived tumor organoids (PDOs) have recently emerged as robust preclinical models. However, few studies were published on lung cancer organoid. This study aims to describe the genomic characteristics of PDOs as a disease model of NSCLC. Samples from resected tumors were collected for organoid culture. DNA was extracted from tumor, organoids and matched PBLs samples and sequenced with whole-exome sequencing. Seven pts were enrolled, including six LUAD (86 %) and one LUSC (14 %). A total of 1625 somatic mutations were detected in tumors. TP53 (71%), EGFR (43%), and KRAS (29%) mutated most frequently in this cohort, and occurred with frequencies of (57%), (43%) and (29%) in matched PDOs. Based on gene catalog related to lung cancer, the median consistency between tumor and organoid was 87 % (0% ∼ 100%). Sample purity was significantly positively related to the variant allele frequency (r=0.82, P=0.0005), and may result in the inconsistence between paired samples. Besides, number of driver gene showed no difference between first- and second-generation organoids.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This study firstly revealed genomic landscape of NSCLC organoid. In spite of heterogeneity, driver mutations presented high consistency between PDOs and paired tumor. Further study is continuing to evaluate outcomes from patients enrolled.

Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development. We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters. We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors. NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTEN mutations, as well as chromosome 18q loss are associated with rapid progression.