4064 Background: Concurrent chemoradiotherapy plus PD-1 blockade is standard for locally advanced esophageal squamous cell carcinoma (ESCC), but its role in advanced disease remains undefined. We investigated the safety and efficacy of Toripalimab combined with chemotherapy and radiotherapy (RCIT) as first-line treatment for advanced ESCC, analyzing long-term survival, recurrence patterns, and immune biomarkers. Methods: This single-arm, phase II trial enrolled treatment-naïve patients with stage IV ESCC (N3 nodal or oligometastases; 5 lesions in 3 organs). Treatment comprised induction chemoimmunotherapy (2 cycles) followed by concurrent radiotherapy (Cycles 3-4) and maintenance immunotherapy. Patients received Paclitaxel (135-175 mg/m2) and Carboplatin (AUC 4-6) plus Toripalimab (240 mg) on day 1 (Q3W). Intensity-modulated radiotherapy (50-50.4 Gy/25-28f) targeted primary/regional lesions, while SBRT (30-40 Gy/3-5f) targeted oligometastases. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), recurrence patterns, health-related quality of life (HRQOL), and biomarker analysis via multiplex immunofluorescence (mIF). Results: Thirty-three patients were enrolled. At a median follow-up of 33.4 months, the 2-year PFS and OS rates were 30.3% (95% CI: 18.1-50.8) and 48.5% (95% CI: 34.1-68.9), respectively. In the efficacy-evaluable population completing radiotherapy (n = 26), outcomes were significantly superior to those who did not, with a median OS of 27.4 months and a 2-year OS of 61.5% (HR = 0.26, p = 0.004). Recurrence occurred in 26 (78.8%) patients, comprising locoregional only (27.3%), distant only (18.2%), and combined failure (33.3%). Notably, among patients completing RT, in-field recurrence (57.7%) remained a predominant failure pattern despite multimodal therapy. HRQOL analysis demonstrated significant post-induction improvement in pain and social functioning scores, whereas radiotherapy transiently worsened dysphagia at 3 months post-RT (p = 0.041). Translational analysis revealed that high baseline tumor infiltration of CD8+ T cells, PD-L1+ dendritic cells, and PD-L1+ macrophages, alongside elevated serum IL-4, IL-17, and IFN-γ\gamma, were significantly associated with long-term survival (OS ≥24 months; p < 0.05). Conclusions: First-line RCIT yields promising long-term survival in advanced oligometastatic ESCC, particularly in patients completing the full radiotherapeutic course, achieving a 2-year OS of 61.5%. However, high rates of in-field recurrence suggest a need for further optimization of local control strategies. Baseline immune infiltrates and cytokine profiles offer potential predictive value for patient stratification. Randomized trials are warranted to validate these findings. Clinical trial information: ChiCTR2100046715.

Purpose:The comparative efficacy of neoadjuvant chemoimmunotherapy (NCIT) vs neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains controversial. Methods and materials:This multicenter retrospective cohort study included patients with LA-ESCC who received NCIT or NCRT followed by esophagectomy across 7 Chinese medical centers between January 2012 and January 2024. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was utilized to balance baseline covariates. Results:Among 2535 enrolled patients, 1414 received NCIT and 1121 received NCRT. After 1:1 PSM, 1258 patients (629 per group) were evaluated. With a median follow-up of 32.7 months, no significant differences were observed between the NCIT and NCRT groups in DFS (hazard ratio [HR], 1.14; 95% CI, 0.94-1.38; P = .20) or OS (HR, 0.98; 95% CI, 0.77-1.25; P = .89). The 2-year DFS rates were 68.7% (NCIT) vs 72.0% (NCRT), and 2-year OS rates were 81.3% vs 83.7%, respectively. NCIT showed a trend toward improved distant metastasis-free survival (DMFS) (HR, 0.87; 95% CI, 0.69-1.11; P = .27), whereas NCRT was associated with a trend toward improved locoregional recurrence-free survival (LRFS) (HR, 1.22; 95% CI, 0.96-1.56; P = .11). Conclusions:NCIT and NCRT demonstrated comparable DFS and OS. These findings suggest that both modalities are valid neoadjuvant strategies, possessing differing strengths in local vs systemic tumor control. These observations await confirmation in prospective trials.

e16138 Background: Patients with esophageal squamous cell carcinoma (ESCC) who fail to achieve a pathological complete response (pCR) following neoadjuvant therapy face a poor prognosis. While adjuvant immunotherapy is a standard of care, alternative strategies are needed for diverse patient populations. We evaluated the efficacy and safety of adjuvant anlotinib, a multi-target tyrosine kinase inhibitor, in ESCC patients with residual pathologic disease. Methods: This prospective, single-arm, phase II trial enrolled patients with locally advanced ESCC harboring residual disease (≥ypT1 and/or ypN+) following neoadjuvant therapy (chemoradiotherapy, chemotherapy, or chemoimmunotherapy) and R0 resection. Patients received oral anlotinib (12 mg once daily; 2 weeks on/1 week off) for up to 8 cycles. The primary endpoint was the 6-month progression-free survival (PFS) rate. Secondary endpoints included safety (CTCAE v5.0), overall survival (OS), and treatment completion rate. Survival outcomes were estimated using the Kaplan-Meier method. Results: From December 2023 to January 2026, 17 patients were enrolled (study terminated early due to slow accrual; planned N = 39). All patients were male (median age: 63.0 years). Preoperative regimens included chemoradiotherapy (35.3%, 6/17), chemoimmunotherapy (23.5%, 4/17), chemotherapy (17.6%, 3/17), and chemoradiotherapy plus immunotherapy (23.5%, 4/17). All patients received anlotinib and comprised the safety/efficacy population (median follow-up: 10.2 months). The most common treatment-related adverse events were hand-foot syndrome (29.4%, 5/17) and diarrhea (29.4%, 5/17), all of which were grade 1-2. Grade 1 hypertension was reported in 1 patient (5.9%). No grade ≥3 adverse events were observed. Eleven patients (64.7%) completed 8 cycles; 3 (17.6%) discontinued due to toxicity, and 3 (17.6%) remained on treatment at data cutoff. Disease recurrence occurred in 3 patients (17.6%), involving lung, liver, and abdominal lymph nodes. Median PFS was 11.3 months. One death (5.9%) occurred; median OS was not reached. The 1-year OS rate was 94.1%. Conclusions: Adjuvant anlotinib demonstrated a highly favorable safety profile and promising preliminary efficacy in ESCC patients with residual disease. Despite the limited sample size, anlotinib represents a viable, chemotherapy-free adjuvant option that may complement current immunotherapy strategies. Further investigation is warranted. Clinical Trial Registration: MR-51-23-050661 (National Healthcare Security Information Platform Medical Research Registration and Filing System) Clinical trial information: MR-51-23-050661. Clinical trial information: MR-51-23-050661 .

Esophageal cancer presents a formidable global health challenge, particularly when complicated by esophageal fistulas, which historically confer a dismal prognosis and severely limit therapeutic options. We report a challenging case of locally advanced esophageal squamous cell carcinoma (ESCC) complicated by an esophageal fistula that ultimately achieved a pathological complete response (pCR). The patient, a male in his 50s, presented with cough and dysphagia and was diagnosed with Stage IVA ESCC. Notably, an esophageal fistula was identified at the initial presentation, posing a threat to treatment. Aggressive enteral nutritional support via nasogastric tube placement and subsequent percutaneous endoscopic gastrostomy (PEG) was promptly initiated. This allowed the patient to successfully complete neoadjuvant therapy consisting of the anti-PD-1 antibody tislelizumab, paclitaxel, carboplatin, and concurrent intensity-modulated radiation therapy (IMRT). Following this multimodal regimen, the patient was reassessed as resectable following response to therapy status. Subsequent radical esophagectomy revealed no residual tumor cells in the primary lesion or dissected lymph nodes (ypT0N0M0), confirming pCR. Immunohistochemical analysis of pre-treatment biopsies demonstrated PD-L1 positivity and high infiltration of CD8+ T cells, suggesting that a robust immune-active microenvironment favored the efficacy of PD-1 blockade. This case underscores the feasibility of integrating immunotherapy with chemoradiotherapy in ESCC patients complicated by esophageal fistulas when supported by rigorous nutritional management.

4066 Background: Locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients with non-clinical complete response (non-CCR) after neoadjuvant chemoradiotherapy (NCRT) face >50% recurrence risk with direct surgery (DS), yet no standardized bridging strategy exists. This first study evaluates the efficacy and safety of sequential chemo-immunotherapy (SCI) as a bridge to surgery in this population. Methods: In this phase 2 cohort study (NCT05189730), 169 LA-ESCC pts who underwent NCRT were prospectively enrolled from June 2021 to January 2025. The NCRT regimen included paclitaxel and carboplatin every 3 weeks for two cycles. Concurrent radiotherapy (40–41.4 Gy) was administered. Post-NCRT, patients were assessed for non-CCR and stratified into two groups: the SCI group received two additional cycles of chemotherapy and tislelizumab (200 mg intravenously every 3 weeks) before surgery, while the DS group proceeded to surgery. The primary endpoint was pCR rate, secondary endpoints included major pathological response (MPR) rates and safety. Results: Eighty-seven non-CCR pts were included (SCI: n = 54; DS: n = 33). The median age was 63 years, with 78.0% male patients. Most patients were stage IIIB(83.9%). Surgery rates were 85.2% in the SCI group (46/54) and 81.8% in the DS group (27/33). In the ITT population, SCI significantly improved pCR rates (40.7% [22/54] vs. 18.1% [6/33]; OR: 3.06, p = 0.024, , one-sided Fisher's Exact Test) and showed a trend toward higher MPR rates (51.8% [28/54] vs. 33.3% [11/33]; OR: 2.14, p = 0.071). In the PP population, pCR rates remained higher in SCI (47.8% [22/46] vs. 22.2% [6/27]; OR: 3.16, p = 0.026) and showed higher MPR rates (60.9% [28/46] vs. 40.7% [11/27]; OR: 2.02, p = 0.078) . At 12 months, PFS rates were 95.6% in the SCI group versus 77.3% in the DS group (p = 0.094) in the ITT population, and 97.4% versus 77.8% (p = 0.064) in the PP population. SCI-related adverse events included lymphopenia (97.7%), leukopenia (84.6%), and fatigue (50.0%). In the no-surgical pts in SCI group, three cases experienced immune pneumonitis and thyroid dysfunction, respectively. Treatment-related adverse events in the SCI group included lymphopenia (97.7%), leukopenia (84.6%), and fatigue (50.0%).The main postoperative complications in the SCI group and DS group were anastomotic leakage and recurrent laryngeal nerve injury (3/46 vs. 2/27, P = 0.629). No significant treatment-related adverse events occurred in the SCI group. Conclusions: This pioneering study demonstrates that SCI as a bridging strategy significantly improves pCR rates by >2-fold (OR>3) and shows promising PFS trends with manageable toxicity in non-CCR LA-ESCC, challenging the immediate surgery paradigm. These results warrant validation in randomized phase 3 trials to redefine standard-of-care. Clinical trial information: NCT05189730 .

Table S4 shows reagents and antibodies.

Figure S7 shows fecal microbial transplantation (FMT) influenced the immune microenvironment of subcutaneous xenograft tumor tissues.

Table S3 shows clinical characteristics of feces providers for fecal microbiota transplantation.

Figure S1 shows detection of intra-tumoral microbiota in the ESCC tissues.

Table S2 shows clinical characteristics of patients with esophageal squamous cell carcinoma (ESCC) who underwent NACI1 treatment.

Figure S8 shows intra-tumoral bacterial contents were stable during tumor growth.

Supplementary figure legend

Figure S2 shows intra-tumoral microbial diversity of patients with ESCC.

Purpose: Radiotherapy-induced oral mucositis is the most common side effect in nasopharyngeal carcinoma (NPC) patients. We aimed to evaluate the efficacy and safety of Rabdosia rubescens drop pills in NPC patients with radiation-induced oral mucositis (RTOM). Methods: The study involved 40 NPC patients who were given Rabdosia rubescens drop pills thrice daily from the start of radiation therapy. The study monitored the incidence and severity of oral mucositis and oral pain. The main outcomes measured were the occurrence rate of oral mucositis, grade 3 oral mucositis, oral pain assessment, and changes in immunological function, body weight, BMI, NRS2002, and albumin levels. Results: In the study, 38 patients completed the treatment. The incidence rates of Grade 0 to 3 oral mucositis were 5.26%, 21.05%, 47.37%, and 26.32% respectively. Pain levels were mild (42.11%), moderate (13.16%), and severe (13.16%). The onset of Grade 1, 2, and 3 oral mucositis occurred at 18, 24, and 30 days respectively. Grade 3 oral mucositis was associated with body weight, BMI, NRS2002 score, and albumin levels. Post-treatment, there was a decrease in CD4 + /CD8 + , CD3 + , and CD4 + immune cells, but an increase in CD8 + cells. Mild to moderate gastrointestinal adverse events were observed in 13.2% of patients. Conclusion: Rabdosia rubescens drop pills administration can reduce the incidence and severity of radiotherapy induced oral mucositis. Our finding suggested a positive impact of Rabdosia rubescens drops pills upon administration to NPC patients.

Brain metastases (BM) represent a highly aggressive, clinically distinct subtype of lung cancer, often associated with poor prognosis. Historically, treatment options for BM have been limited and largely nonspecific. However, recent advancements in clinical and preclinical research have led to substantial improvements in patient outcomes. This review focuses on BM arising from lung cancer, providing an overview of recent findings related to clinical characteristics, diagnostic strategies, and early metastatic processes. Multi-omics analyses have elucidated the molecular mechanisms underlying tumor initiation and progression, with particular emphasis on the role of the tumor microenvironment. In this review, preclinical BM models, detailed signaling pathways, and emerging clinical therapies are also discussed. Current treatment approaches are multidisciplinary, and multi-omics technologies enhance both diagnosis and therapeutic strategies by revealing the complex biology of BM. Continued research is needed to identify BM-specific drug targets, particularly those involved in crossing the blood-brain barrier and remodeling the brain microenvironment. Addressing these challenges is crucial for improving clinical outcomes in patients with BM.

Table S5 shows sequences of the primers used for qRT-PCR.

Figure S5 shows intra-tumoral Microbiota associated with activated immune cell infiltration.

Figure S4 shows intra-tumoral bacteria identified in patients with ESCC.

8044 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare form of squamous lung cancer, and large-scale clinical studies on its clinical features, prognosis at different stages, and outcomes following treatments are limited. Methods: Patients with PLELC diagnosed by pathology from January 2009 to December 2023 at Sichuan Cancer Hospital and Sun Yat-sen University Cancer Centre were retrospectively analysed. Survival curves were estimated using the Kaplan-Meier method, Log-rank tests were used to compare differences between groups, and the Bonferroni method was used to correct the p-value when two-by-two comparisons between multiple groups were involved. Results: A total of 1,106 PLELC patients were included in the study. Most patients were non-smokers (73.4%), and brain metastasis was rare (0.3%). Tumor-specific characteristics showed a low incidence of EGFR mutation (0.6%) but a high prevalence of PD-L1 positivity (71.6%). The median follow-up duration was 31.6 months. The two-year overall survival (OS) rates for stage I, II, III, and IV patients were 99.4%, 97.7%, 92.7%, and 70.4%, respectively, while the five-year OS rates were 94.8%, 88.7%, 70.6%, and 37.8%, respectively. No statistically significant differences in progression-free survival (PFS) or OS were observed between surgery alone and surgery combined with adjuvant therapy in stage I and II patients, or between radiochemotherapy and combined surgery-radiochemotherapy in stage IIIA and IIIB patients. However, in stage IV patients, chemotherapy combined with immunotherapy resulted in significantly better PFS and OS compared to chemotherapy alone. Conclusions: PLELC patients, mostly non-smokers with rare brain metastasis and high PD-L1 positivity, show favorable prognosis, but further research is needed to refine its optimal treatment strategies. PFS and OS in patients with different stages. Stage Number of cases Median PFS (months) 2-year PFS 95% CI 5-year PFS 95% CI Median OS (months) 2-year OS 95% CI 5-year OS 95% CI IA 145 108.3 94.0% 88.9%-99.1% 75.6% 63.2%-88% Incalcu 99.1% 97.3%-100% 95.7% 90.7%-100% IB 56 119.2 78.0% 65.3%-90.7% 65.2% 49.5%-80.9% Incalcu 100.0% 100%-100% 93.5% 84.8%-100% IIA 37 Incalcu 85.4% 70.1%-100% 62.9% 40.9%-85% Incalcu 100.0% 100%-100% 96.2% 88.8%-100% IIB 104 87.9 78.0% 68.6%-87.4% 60.0% 47.2%-72.8% Incalcu 96.9% 93.6%-100% 85.6% 77.1%-94.1% IIIA 213 47.9 70.6% 63.5%-77.7% 42.8% 33.9%-51.7% 161.5 97.9% 95.9%-99.9% 79.7% 72.4%-87% IIIB 132 24.6 51.1% 41.3%-60.9% 21.3% 11.7%-30.9% 83.7 87.9% 81.6%-94.2% 65.3% 54.8%-75.8% IIIC 73 22.0 44.0% 29.5%-58.5% 24.7% 8.4%-41% 53.5 84.9% 75.3%-94.5% 49.4% 31.8%-67% IVA 123 12.0 29.8% 20.4%-39.2% 0.0% 0%-4.5% 50.0 79.3% 70.9%-87.7% 44.1% 30.9%-57.3% IVB 223 9.0 16.0% 10.3%-21.7% 2.7% 0%-6% 33.6 65.4% 58.1%-72.7% 34.1% 24.3%-43.9% Incalcu: Incalculable; CI: confidence interval.