Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in‐depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis. It is still being explored in depth due to its complex molecular mechanisms of occurrence and development. Lipids play a crucial role in cells by participating in energy supply, biofilm formation, and signal transduction processes, and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors. More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning, progress, and treatment resistance. The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism. Therefore, we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer, and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer, as well as its significance in exploring potential therapeutic targets and biomarkers.

Radiation pneumonitis (RP) is a prevalent complication associated with lung cancer radiotherapy; nonetheless, its effects on lung cancer immunotherapy and the underlying biological mechanisms remain inadequately elucidated. Utilizing mouse models of RP and orthotopically lung cancer, we witnessed immunotherapy-enhanced liver metastasis of lung cancer within the context of RP, accompanied by increased neutrophil infiltration of the primary tumor. Analysis of metabolic adaptations driven by the inflammatory microenvironment during treatment revealed that RP and immunotherapy act synergistically to exacerbate lipid metabolic dysregulation and oxidative stress. Integrating clinical validation with single-cell RNA sequencing data from a multicenter lung adenocarcinoma cohort, we demonstrated that elevated oxidative stress scores within tumor tissue were significantly associated with both diminished response to immunotherapy and unfavorable clinical outcomes. These findings coincided with alterations in the tumor immune microenvironment, notably a marked increase in neutrophils and activated mast cells. This investigation highlights that RP is not merely a toxicity but an active modulator of the tumor-immune-metabolism landscape. By dissecting the RP-ICB-metabolism axis, we have elucidated a novel mechanism underlying immunotherapy resistance, offering new insights into the rational design of optimized radioimmunotherapy.

Purpose: This study evaluates the impact of thoracic radiotherapy (TRT) combined with immune checkpoint inhibitors (ICIs) treatment-related pneumonitis on tumor progression and prognosis in patients with non-small cell lung cancer (NSCLC).Methods: Data were collected retrospectively from NSCLC patients treated with TRT and ICIs between January 2019 and August 2023. Treatment-related pneumonitis (TRP) was assessed and graded using the Common Terminology Criteria for Adverse Events (CTCAE) and the Chinese Society of Clinical Oncology Guidelines for Managing Immunotherapy-Related Toxicities. Kaplan-Meier curves and log-rank tests examined associations between pneumonitis with local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). COX regression identified prognostic factors in the pneumonitis group.Results: Among 86 patients, 58 (67.4%) developed TRP, including 37.2% with grade 2 pneumonitis, and no grade ≥3 cases. 12 patients (14.0%) developed mixed radiation and ICIs pneumonitis. The pneumonitis group had significantly shorter DMFS (12.07 vs not reached, p = 0.028) and PFS (9.53 vs 14.27 months, p = 0.040), shorter LRFS compared to the non-pneumonitis group, but similar OS. High-grade pneumonitis correlated with worse outcomes, especially DMFS (p = 0.031), basically no differences among pneumonitis types. Multivariate COX analysis identified solitary pulmonary nodules or masses as independent negative prognostic factors for PFS, while higher MLD (mean lung dose) independently predicted reduced OS.Conclusion: Pneumonitis resulting from TRT combined with ICIs was associated with shorter PFS but did not affect OS in NSCLC patients. Mixed pneumonitis did not worsen outcomes. Larger prospective studies are needed to validate these findings.

Background: Uncommon epidermal growth factor receptor (EGFR) gene mutant locally advanced non-small cell lung cancer (NSCLC) has been poorly documented in the literature. Our study aimed to investigate the clinical features and outcomes associated with these mutations. Methods: A multi-center retrospective study was conducted to review 511 patients with EGFR mutant unresectable stage III lung adenocarcinoma, treated between 2012 and 2018 across 12 Chinese institutions. The patients were categorized into three groups based on their primary treatment: chemoradiotherapy (CRT), EGFR-TKIs (tyrosine kinase inhibitors), and radiotherapy (RT) combined with EGFR-TKIs. Results: Among the 511 patients, 49 (9.6%) had uncommon EGFR mutations. Of these, 37 had detailed systemic treatment information. The uncommon mutations included exon 18 G719X (22.4%), exon 20 insertion (18.4%), exon 20 S768I (8.2%), T790M (8.2%), and exon 21 L861Q (4.1%). Compound mutations were identified in 34.7% of patients. There was a significant difference in progression-free survival (PFS) for uncommon and common mutation group (median 11.9 vs. 17.5 months, P=0.005). However, no significant difference was observed in overall survival (OS, P=0.14). The median PFS for the uncommon mutation group was 11.9 months for CRT (n=12, 32.4%), 5.0 months for EGFR-TKIs (n=16, 43.2%), and 14.8 months for RT combined with TKIs (n=9, 23.4%) (P=0.02). The median OS for the same groups were 43.6 months, 30.9 months, and not reached, respectively (P=0.18). Compared to EGFR-TKIs, both CRT and RT combined with TKIs significantly improved PFS (P=0.02, 0.04, respectively), and showed a trend toward superior OS compared to EGFR-TKIs (P=0.49, 0.06, respectively). Conclusions: This study was the first to systematically summarize the clinical features and outcomes of unresectable locally advanced lung adenocarcinoma, with uncommon EGFR mutations. RT combined with sensitivity EGFR-TKIs may be a promising treatment option, while CRT remains the primary treatment choice.

MF-gel weaves cellulose microfibers into gelatin hydrogel to recapitulate the structural architecture of natural collagen fiber bundles, expanding patient lung cancer organoids while preserving invasion, histopathology, mutations and drug response.