Prognostic impact of advanced lung cancer inflammation index and tumor load index in esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy

Background: Esophageal squamous cell carcinoma (ESCC) carries a high risk of recurrence after neoadjuvant immunochemotherapy and surgery. Both host inflammatory-nutritional status and circulating tumor markers may jointly influence clinical outcomes. We evaluated the prognostic value of the Advanced Lung Cancer Inflammation Index (ALI) and a composite Tumor Load Index (TL) to refine risk stratification in this setting. Methods: We retrospectively analyzed 460 consecutive ESCC patients who received 2-3 cycles of PD-1 inhibitor plus platinum/taxane-based chemotherapy followed by esophagectomy. ALI was calculated as BMI × albumin/NLR. TL was derived via LASSO Cox regression from pre-treatment SCC-Ag, CEA, and CA19-9. Optimal cutoffs were identified using maximally selected rank statistics (ALI: 31.22; TL: 0.224). Patients were categorized as low-risk (high ALI/low TL), intermediate-risk (high ALI/high TL or low ALI/low TL), and high-risk (low ALI/high TL). Endpoints included overall survival (OS), disease-free survival (DFS), pathologic complete response (pCR), and major pathologic response (MPR). Results: With a median follow-up of 42 months, 3-year OS rates were 84.7%, 66.0%, and 34.6% for the low-, intermediate-, and high-risk groups, respectively (log-rank P < 0.001). Corresponding 3-year DFS rates were 75.4%, 61.6%, and 29.0%. In multivariable Cox models, intermediate- and high-risk groups had progressively worse OS (adjusted HR = 2.11 and 3.43) and DFS (adjusted HR = 1.64 and 2.62) compared with the low-risk reference (all P < 0.01). High-risk status independently predicted lower odds of achieving MPR (adjusted OR = 0.34, P = 0.002) and pCR (OR = 0.07, P = 0.011). A prognostic nomogram integrating risk group, ASA score, MPR, and ypN status showed strong discrimination (C-index = 0.742) and favorable calibration for 2-, 3-, and 4-year OS, with time-dependent AUCs of 0.759, 0.789, and 0.712. Conclusions: Pre-treatment ALI and TL jointly provide robust and complementary prognostic information in ESCC patients receiving neoadjuvant immunochemotherapy. Low ALI combined with high TL identifies a biologically aggressive subset with poor pathologic response and inferior survival. Integration of ALI and TL may facilitate risk-adapted perioperative strategies and personalized treatment optimization.