2288 - Efficacy and Prognosis of Neoadjuvant Chemoimmunotherapy Followed by Concurrent Chemoradiotherapy in Unresectable Esophageal Cancer: The First Single-Center Real-World Study

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 26

POSTER

Presenter(s)

Xiaofei Zhang, MD - Shanghai cancer hospital, Shanghai, shanghai

X. Zhang¹, W. Zhao¹, K. Zhao², and H. Lu³; ¹Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, ³the Second People’s Hospital of Yichang, Yichang, Hubei, Christmas Island

Purpose/Objective(s): The optimal treatment for unresectable esophageal cancer (EC) remains unclear. This is the first real-world study on neoadjuvant chemoimmunotherapy followed by concurrent chemoradiotherapy (CCRT).Assess efficacy, safety, prognostic factors of this sequential therapy in unresectable EC, and establish a prognostic stratification model.

Materials/Methods: Eighty-eight consecutive patients (76 squamous, 12 non-squamous; 42 stage II/III, 46 IVA/IVB; median age 70 years; 83.0% male) received neoadjuvant chemoimmunotherapy + CCRT; adjuvant therapy was investigator-dependent. Survival analyses used Kaplan-Meier and Cox regression; a death risk scoring system was developed via hazard ratios (HR).

Results: Median follow-up 28 months. Two-year OS/RFS: 78.5%/76.1%; median RFS 28.4 months. Best ORR 48.9%, DCR 95.5% (ORR post-radiotherapy: 64.8%?57.9%). Recurrence occurred in 21 (23.9%) patients (median 9.2 months); 52.4% were distant metastases (liver/bone most common). Stage IV patients had earlier recurrence (6.8 vs. 10.4 months, p=0.045) and higher distant metastasis rates (62.5% vs. 46.2%). Grade =3 adverse events (AEs): 25.0% (mainly hematologic, 11.4%); no treatment-related deaths. =3 CCRT cycles increased grade =3 hematologic toxicity (31.8% vs. 19.6%, p=0.048) without efficacy benefit. Independent recurrence risk factors: non-squamous histology (HR=3.12, p=0.006), stage IV (HR=2.45, p=0.019); protective factors: adjuvant immunotherapy =5 cycles (HR=0.39, p=0.006), CCRT (HR=0.43, p=0.033). Independent mortality risk factors: stage IV (HR=2.98, p=0.014), non-squamous histology (HR=2.87, p=0.024); protective factor: adjuvant immunotherapy =5 cycles (HR=0.36, p=0.008). Age =70 showed a trend (HR=1.68, p=0.19). C-index: 0.78 (recurrence), 0.81 (death). Optimal neoadjuvant chemoimmunotherapy cycles: 3–4 (ORR 65.6%, recurrence 18.8%); no benefit beyond 5. Adjuvant immunotherapy dose-dependent benefit: recurrence rates 36.4% (0 cycles), 21.4% (1–4), 11.1% (5–12).

Prognostic scoring system (death risk): stage IV (+2), non-squamous (+2), age =70 (+1), adjuvant immunotherapy =5 cycles (–3). Five risk strata: very low (=–2): 2-year OS >90%; low (–1–0): 85–90%; intermediate (1–2): 70–85%; high (3–4): 50–70%; very high (=5): <50%.

Conclusion: Neoadjuvant chemoimmunotherapy followed by CCRT is effective and safe for unresectable EC. Adjuvant immunotherapy (=5 cycles) is the strongest modifiable protective factor. Non-squamous histology (poor immunotherapy response) and stage IV (early recurrence/distant metastasis) are key risk factors, requiring individualized strategies and intensive 6-month surveillance. Optimal cycles: 3–4 neoadjuvant chemoimmunotherapy, 1–2 CCRT. The four-factor scoring system effectively stratifies risk to guide personalized treatment/follow-up. Limitations: single-center retrospective design, small non-squamous sample, lack of biomarkers; prospective validation needed.