Esophageal cancer is the sixth leading cause of cancer-related deaths (1). Over half of the new esophageal cancer cases occur in China (2), with esophageal squamous cell carcinoma (ESCC) being the predominant pathological type (3). Available treatment options include surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and their combinations. However, the prognosis remains poor, with a very low overall 5-year survival rate, especially among older people (3). Although achieving effective treatment remains challenging, recent advances in immunotherapy and targeted therapies have demonstrated promise for improving outcomes (4–6).

Concurrent chemoradiotherapy (CRT) remains the cornerstone treatment for locally advanced esophageal cancer, providing superior local tumor control and survival benefits compared to radiotherapy alone (7–9). The CROSS trial established paclitaxel plus carboplatin as a preferred definitive CRT regimen, demonstrating improved overall survival (OS) and disease-specific survival in both preoperative and unresectable settings (10, 11). Additionally, the RTOG 85-01 trial confirmed the benefits of CRT with fluorouracil plus cisplatin, reporting a median survival advantage (14 vs. 9 months) and significantly improved 5-year OS (27% vs. 0%) over radiotherapy alone, with sustained survival benefits at 8 and 10 years. CRT also enhances local tumor control, reducing local failure rates (47% vs. 65%) compared to radiotherapy alone. These findings underscore CRT’s pivotal role in improving long-term outcomes in esophageal cancer (7, 8).However, CRT-related toxicities, particularly radiation-induced esophagitis and myelosuppression, often lead to treatment discontinuation or suboptimal dosing, limiting its efficacy in elderly or frail patients (12–14). In recent years, the integration of immunotherapy and targeted therapy has emerged as a strategy to enhance tumor response and mitigate resistance mechanisms (6, 15). Preclinical and clinical studies suggest that EGFR-targeted agents, such as nimotuzumab—an anti-EGFR monoclonal antibody—may enhance radiosensitivity (16, 17). Despite these advancements, the optimal strategy for combining CRT with immunotherapy and targeted agents remains undefined, necessitating further clinical investigation into novel treatment paradigms.

This case report describes the use of sintilimab, low-dose-rate chemoradiotherapy, and nimotuzumab for the curative treatment of an older patient with advanced esophageal squamous cell carcinoma, followed by maintenance therapy with immunotherapy and anti-angiogenesis treatment. In this case, immunotherapy played a central role throughout treatment. The use of low-dose radiotherapy helped reduce radiotherapy-related side effects and improve patient tolerance. Preclinical studies suggest that LDRT enhances immune responses by promoting tumor antigen release, increasing T cell infiltration, and modifying the tumor microenvironment, potentially improving tumor control when combined with immunotherapy (18). Recent clinical studies have further supported these findings, demonstrating that radiotherapy plus PD-1 inhibitors significantly improve progression-free and overall survival in advanced solid tumors (19). These data reinforce the potential of combining LDRT with immunotherapy to optimize treatment efficacy in esophageal cancer. Additionally, the concurrent use of albumin-bound paclitaxel and nimotuzumab as radiosensitizing agents during weekly radiotherapy sessions contributed significantly to improving chemotherapy sensitivity. The patient achieved progression-free survival for 17 months and survived for over 35 months without reaching the endpoint. These findings suggest the potential of this combination to improve efficacy while maintaining tolerability, particularly in older patients.

On September 26, 2024, during a follow-up with the family of the patient, they reported that the patient was very satisfied with the treatment outcomes. The current condition was stable, and the patient could eat normally on their own, although the swallowing speed was slightly reduced.

The treatment of advanced ESCC remains a significant clinical challenge owing to the poor prognosis and limited efficacy of conventional therapies. In recent years, the advent of immunotherapy, particularly immune checkpoint inhibitors targeting programmed cell death protein-1/programmed death-ligand 1 pathway, has provided a new therapeutic avenue for patients with advanced ESCC (4, 5, 20).

Definitive concurrent chemoradiotherapy has been suggested as the primary treatment for patients with unresectable disease or for those who are medically unfit for surgery. In the setting of Definitive concurrent chemoradiotherapy, the Radiation Therapy Oncology Group 85-01 trial recommended 50 Gy in 25 fractions as the standard radiation dose (8, 21). According to the 2019 Chinese Society of Clinical Oncologyguidelines, radiotherapy or chemoradiotherapy is still advised for older patients or those with poor cardiopulmonary function or multiple comorbidities who are not candidates for surgery. Radiotherapy is an effective option for alleviating clinical symptoms such as bleeding, pain, and dysphagia in advanced ESCC and for improving the quality of life, nutritional status, and survival outcomes. One study confirmed that in older patients with esophageal carcinoma who are not candidates for surgery, concurrent chemoradiotherapy with a maximum total radiation dose of 63 Gy (5 ×1.8 Gy/week) results in significantly better treatment outcomes than radiotherapy alone (22).

In the present study, definitive chemoradiotherapy was initially considered. However, the extensive involvement of the tumor, including airway invasion, along with a history of anlotinib treatment and significant dysphagia, posed challenges. The patient refused a gastrostomy for nutritional support, and conventional fractionated chemoradiotherapy carries a high risk of esophagotracheal fistula formation. Additionally, concern existed that the patient might not tolerate the side effects of the treatment, potentially leading to discontinuation.

According to previous studies, low-dose radiotherapy combined with modified chemotherapy using a continuous low-dose regimen can improve treatment compliance and promote fistula healing in patients with esophageal cancer complicated by esophagotracheal fistulas (23, 24). Low-dose radiotherapy of 60 Gy (5 ×1.2 Gy/week) in 50 fractions was administered in the present study, reducing the per-fraction dose and extending the treatment duration to prevent the tumor from shrinking too rapidly while allowing for normal tissue repair. This approach helped to minimize the risk of acute radiation-induced mucositis and perforation. Our goal was to ensure that a sufficiently high cumulative dose would still offer a chance for tumor control. Older patients have poor tolerance to standard dual-drug chemotherapy; therefore, for concurrent chemotherapy, weekly albumin-bound paclitaxel at 100 mg was used owing to its relatively low toxicity profile (25).

Preclinical studies have revealed that Nimotuzumab, a humanized monoclonal antibody that targets epidermal growth factor receptor, enhances radiosensitivity by promoting radiation-induced apoptosis (26). In the intent-to-treat population, the endoscopic complete response rates were 47.2% with nimotuzumab and 33.3% without nimotuzumab (P = 0.17), whereas the combined endoscopic complete response and pathologic complete response rates were significantly higher with nimotuzumab at 62.3% compared to 37.0% without it (P = 0.02). Nimotuzumab combined with chemoradiotherapy can achieve better complete response rates, extend survival, and does not increase adverse effects (16, 27). Recent findings suggest that the combination of nimotuzumab with radiotherapy is well tolerated and produces favorable outcomes in older patients with unresectable esophageal cancer (17). To further enhance the radiosensitization effect of the treatment and considering the financial capacity of the patient, we added nimotuzumab 50 mg/week was added as a targeted therapy in this study.

Recent breakthroughs in immunotherapy have presented new avenues for the treatment of advanced ESCC (4, 5, 20). Studies such as KEYNOTE-181 and ATTRACTION-03 have demonstrated significant survival benefits of programmed cell death protein -1 inhibitors, including pembrolizumab and nivolumab, establishing immunotherapy as a viable option for these patients (4, 5). The ORIENT-15 trial further demonstrated that sintilimab combined with chemotherapy offered superior survival outcomes compared with chemotherapy alone, regardless A of programmed death-ligand 1 expression (20). In accordance with the treatment guidelines, second-line sintilimab immunotherapy combined with chemoradiotherapy is recommended. Therefore, in the present study, sintilimab immunotherapy was added in combination with chemoradiotherapy and targeted therapy.

Antiangiogenic therapies are becoming integral to the treatment of esophageal cancer. Anlotinib, a selective Vascular Endothelial Growth Factor receptor 2 inhibitor, has demonstrated strong anti-angiogenic and antitumor effects in preclinical models (28).Based on the ALTER1102 study (29), the 2019 Chinese Society of Clinical Oncology Eophageal Cancer Guidelines recommend anlotinib monotherapy as second-line and beyond in advanced esophageal squamous cell carcinoma. When combined with immunotherapy, anlotinib can reshape the tumor microenvironment and enhance immune cell infiltration and treatment efficacy, showing promise in esophageal cancer and other malignancies (6, 15).At the end of radiotherapy, partial response was achieved according to the Response Evaluation Criteria in Solid tumors criteria 1.1 (30). As a result, a combination of sintilimab and anlotinib maintenance immunotherapy was initiated in January 2022 and continued until June 2022 owing to financial constraints. The tumor recurred in March 2023 and treatment with sintilimab and anlotinib remained effective, with continued disease regression observed in April 2024. A follow-up on September 26, 2024, revealed that the patient was well, with no pain and normal eating ability.

This case report highlights the successful use of low-dose radiotherapy combined with immunotherapy in a patient with stage IVA esophageal cancer, achieving a progression-free survival of 17 months with ongoing overall survival. This treatment minimizes radiotherapy-related side effects, improves tolerability, and enables high-quality survival. Although the financial limitations of the patient required reduced doses of nimotuzumab, this comprehensive strategy proved to be effective. However, additional limitations should be considered. The interaction between LDRT, immunotherapy, and targeted therapy may vary among patients, potentially influencing immune responses. Additionally, while myelosuppression was not severe, mild radiation-induced esophagitis and fatigue were observed, requiring supportive care. Further research is needed to refine the balance between maximizing therapeutic efficacy and minimizing adverse effects.

Due to the financial constraints and poor compliance of the patient, testing for programmed death-ligand 1 and epidermal growth factor receptor expression was incomplete. During the later follow-up period, the patient refused hospitalization and completed only outpatient CT scans. After May 2024, the patient returned to their hometown and was not followed up at our hospital, leaving incomplete imaging data. Current status updates are available only via phone, and further studies are required to confirm the long-term benefits and broader applicability of this approach.