Several studies have evaluated PD-1 inhibitors plus chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), but comparative data with chemoradiotherapy (CRT) remain limited. This multicenter, randomized, open-label, phase 2 non-inferiority trial (REVO, NCT05007145) assessed the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy (ICT) versus CRT in patients with resectable, locally advanced ESCC. A total of 104 patients were randomized to ICT (camrelizumab, nab-paclitaxel, cisplatin) or CRT (nab-paclitaxel, cisplatin, radiotherapy). The primary endpoint was pathologic complete response (pCR). ICT achieved a pCR rate of 32.7% versus 34.6% with CRT (rate ratio 0.94, 90% CI 0.6–1.49), demonstrating non-inferiority and meeting the pre-specified primary endpoint. Major pathologic response was observed in 42.3% of ICT patients and 57.7% of CRT patients, with R0 resection achieved in 100% of both groups. 1-year disease-free survival was 89.1% versus 78.2%, and 1-year overall survival was 100% versus 92.3% for ICT and CRT, respectively. Grade ≥3 treatment-related adverse events occurred in 19.2% of ICT patients and 33.3% of CRT patients, and surgical complications were reported in 31.1% and 35.9%, respectively. These findings indicate that ICT is a safe and effective neoadjuvant strategy for resectable ESCC with a more favorable safety profile.

Background The prognostic value of lymphovascular invasion (LVI) in esophageal cancer remains controversial. This study investigated the impact of LVI on prognosis in thoracic esophageal squamous cell carcinoma (ESCC). Methods A total of 1586 patients who underwent radical esophagectomy were selected for the study. Correlations between LVI and clinicopathological features were evaluated by χ² test. Univariate analysis of the survival curve was conducted using the Kaplan–Meier method. Multivariate analysis was carried out by Cox regression. The Akaike information criterion (AIC) and the concordance index (c‐index) were employed to assess model prognostic accuracy of different pN staging systems. Results The presence of LVI was detected in 406 of 1586 (25.6%) patients. LVI frequency was significantly higher in patients with higher pN classifications (P < 0.001). LVI had independent significant prognostic value in ESCC (P < 0.001). In subgroup analyses, the presence of LVI significantly decreased overall survival in pN0, pN2, and pN3 stage patients. The AIC value of the pN staging system modified by LVI was lower than that of the current pN staging system, while the c‐index of the modified pN staging system was higher than that of the current pN staging system. Conclusion Our results suggest that LVI is an independent prognostic indicator in radically resected thoracic ESCC. LVI could potentially supplement the pN ESCC staging system. ESCC patients with LVI could be staged at more advanced pN classifications.

The six transcriptomic immune subtypes (ISs) (C1 - C6) were reported to have complex and different interplay between TME and cancer cells in TCGA (The Cancer Genome Atlas) pan-cancer cohort. Our study specifically explored how the consequence of interplay determines the prognosis and the response to therapy in LUAD cohorts. Clinical and molecular information of LUAD patients were from TCGA and Gene Expression Omnibus (GEO). The immune cell populations and gene/pathway enrichment analysis were performed to explore the molecular differences among the C3 IS and other ISs in the LUAD population. The proportion of C3 inflammatory IS was identified as the most common IS in both TCGA (N = 457) and GEO (N = 901) cohorts. The C3 IS was also found to be the most accurate prognostic subtype, which was associated with significantly longer OS (p <0.001) and DFS (p <0.001). The C3 IS presented higher levels of CD8 T, M1 macrophage, and myeloid dendritic cells, while lower levels of M2 macrophages and cancer-associated fibroblast cells. Moreover, the C3 subtype was enriched in the antigen process and presenting, interferon-gamma response, T cell receptor signaling, and natural killer cell-mediated cytotoxicity pathways than C1/C2. In contrast, the C1/C2 presented greater activation of pathways related to the cell cycles, DNA repair, and p53 signaling pathways. The immune-related C3 IS had a great ability to stratify the prognosis of LUAD, providing clues for further pathogenic research. This classification might help direct precision medicine screenings of LUAD patients, thus possibly improving their prognoses.

Background: Lung squamous cell carcinoma (LUSC) is characterized by frequent mutations of tumor protein p53 (TP53) and cyclin dependent kinase inhibitor 2A (CDKN2A). However, to date, the impact of TP53/CDKN2A status on the clinical outcome of patients with early-stage LUSC is unclear. Methods: Tissue samples from 16 early-stage, surgically resected LUSCs were analyzed by next-generation sequencing (NGS). Information regarding TP53 and CDKN2A alterations and patient survival time was downloaded from The Cancer Genome Atlas (TCGA) database. The associations between TP53 and CDKN2A status and tumor characteristics, outcomes including overall survival (OS) and disease-free survival (DFS), and mutation counts were investigated. Results: TP53 and CDKN2A exhibited a high frequency of somatic mutations in early-stage LUSC in our center. Data for 1,176 samples were collected from TCGA. CDKN2A mutation status was associated with TP53 mutation status (P=0.040). TP53 mutation was a favorable prognostic factor for early-stage LUSC. The OS times of patients with wild-type and mutated TP53 were 28.94 and 60.48 months, respectively (P=0.002). In contrast, CDKN2A mutations were significantly associated with a shorter survival time in early-stage LUSC. The OS times for wild-type and mutated CDKN2A patients were 62.81 and 37.55 months, respectively (P=0.026). Patients with TP53 mutations had higher total mutation counts compared to patients with wild-type TP53. Furthermore, OS was significantly shorter in patients with a low mutation count compared to patients with a median or high mutation count. Conclusions: Early-stage LUSC patients with TP53 mutations had a longer OS, while those with CDKN2A mutations had a shorter OS. Furthermore, patients with TP53 mutation/CDKN2A wild-type status had a longer OS. CDKN2A mutation is a vital indicator for prognostic assessment according to TP53 status. The prolonged survival of patients with TP53 mutations may be due to their high mutation counts. Larger datasets are required to validate these observations.