Several pathologic characteristics of the primary tumor are correlated with the outcome of esophagectomy for squamous carcinoma of the thoracic esophagus. Patients with fewer than 2 metastatic nodes after curative esophagectomy have a better prognosis than those with multiple involved nodes (>2). To stratify patients appropriately for prognosis, it is necessary to refine the current 6th edition TNM staging system.

Background Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care. Methods We prospectively recruited 128 patients with stage I–III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection. Results The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence. Conclusions Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.

e16029 Background: Compared with neoadjuvant chemotherapy alone，Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.

e15265 Background: Piwi-interacting RNAs (piRNAs) are a novel type of small noncoding RNAs which have important biological functions in malignant diseases. However, little is known about the clinical value of piRNAs in esophageal squamous cell carcinoma (ESCC). Hence, we demonstrated that two representative piRNAs, piR-36026 and piR-651, to dig out their clinical value in ESCC. Methods: Quantitative real-time PCR was employed to detect the levels of piR-36026 and piR-651 expression in ESCC tissues. Furthermore, the correlation between them and ESCC patients' clinicopathological characteristics were explored. Receiver operating characteristic (ROC) curves were constructed for measuring significances of piR-36026 and piR-651 for ESCC diagnosis. Results: Both of piR-36026 and piR-651 were prominently increased in ESCC tissues compared with normal. Additionally, piR-36026 was related with ESCC patients' diameter (P = 0.013), TNM stage (P = 0.027), tumor differentiation (P = 0.008) and CEA (P = 0.013); and piR-651 was associated with diameter (P = 0.005), lymph node metastasis (P = 0.002), tumor differentiation (P = 0.008) and SCC (P = 0.002). The area under the ROC curve (AUC) of piR-36026 was up to 0.8634 (95% confidence interval: 0.8171-0.9089, P < 0.05). Similarly, the AUC of piR-651 was 0.8525 (95% confidence interval: 0.7804-0.9247, P < 0.05). Conclusions: These results demonstrated that both piR-36026 and piR-651 may play a crucial role in ESCC oncogenesis; and they may be diagnostic biomarker for ESCC.