Low-Dose Involved-Field Rt, Plus Immunochemotherapy Showed Excellent Efficacy and Low Toxicities in Unresectable La-Escc: A Prospective Phase Ii Study

Abstract Background Concurrent chemoradiotherapy is recommended for unresectable locally advanced (LA) esophageal squamous cell carcinoma (ESCC). Also, the immune checkpoint inhibitors (ICIs) are being actively explored in ESCC. Here, we propose a combination of low-dose involved-field radiotherapy (RT), camrelizumab, and chemotherapy, in an attempt to both enhancing efficacy and reducing toxicity, in LA-ESCC. Methods This prospective, single-arm, phase II trial (HX-LION, NCT06603402) enrolled patients with unresectable LA-ESCC. The primary endpoint was 1-year PFS (PFS1Y), with secondary endpoints of ORR, OS, and safety. Assuming a PFS1Y of 52% (historical control 34%), and using a two-sided alpha of 0.05 and 80% power, the estimated sample size was 41 (including 10% dropout). Patients received 1 cycle of induction therapy (paclitaxel/nab-paclitaxel, carboplatin, camrelizumab, q3w), followed by RT (45.0 Gy in 25 fractions) starting with the second cycle. CTV was defined as the GTV plus 3 cm longitudinal, 0.5 cm radial, and 0.5 cm for involved lymph nodes. Results Between Aug 2023 and Nov 2024, 38 patients (33 males, 5 females; median age 66, range 44–80) were enrolled. Among 26 evaluable patients, the 1-year PFS rate was 75%, and the ORR was 96.2%. At a median follow-up of 8.5 months, median PFS and OS were not reached (Fig. 1). Treatment-related adverse events (TRAEs) occurred in all patients, with G3–4 TRAEs in 63.2%, mainly myelosuppression. Other G3–4 events included infectious pneumonia (n = 2), pneumonitis (n = 1), and bowel obstruction (n = 1). No treatment-related deaths occurred. Common TRAEs included esophagitis (28.9%) and decreased appetite (23.7%). Conclusion Our combination of low-dose involved-field RT, camrelizumab, and chemotherapy showed excellent efficacy, together with acceptable and manageable toxicities in unresectable LA-ESCC. Ongoing follow-up and additional patient recruitment are planned to further these findings. Clinical trial information: NCT06603402. Research Sponsor: None.