Efficacy of dendritic cell-cytokine-induced killer immunotherapy plus intensity-modulated radiation therapy in treating elderly patients with esophageal carcinoma

Esophageal squamous cell carcinoma

Esophageal Squamous Cell Carcinoma

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Summary

This study investigates the clinical efficacy of cytokine-induced killer cell (CIK) and Dendritic Cell (DC) Therapy in addition to intensity-modulated radiation therapy (IMRT) for treating elderly patients with esophageal carcinoma (EC). As a result, the therapy could improve patients’quality of life and immune function, decrease bone marrow suppression, and lengthen survival time.

Patients characteristics

A total of 68 patients (45 male and 23 female) with squamous cell carcinoma of the esophagus were included in this study. The patients were aged 65-79 years, with a median age of 70 years. Among these patients, the numbers of patients diagnosed with stage I, II, III, and IV EC were 3, 12, 29, and 24, respectively, according to the tumor-node-metastasis system.
The inclusion criteria were as follows: 1) pathologically and cytologically confirmed EC; 2) age ≥ 65 years and a Karnofsky score ≥ 70; 3) no history of antitumor therapy prior to this study; 4) no anomalies in routine blood, hepatic function, and renal function testing; 5) no severe heart, hepatic, or kidney disease; and 6) measurable tumor lesions.

Methodology

2 days before IMRT, peripheral blood mononuclear cells were suspended in a medium containing IL-2, CD3, and IFN-γ to culture CIK cells. After continuous passage, the cells that adhered to the flasks were removed with a cell spatula and centrifugation at 3500 rpm at 25°C. Then, the cells were suspended in DC-CIK medium containing IL-2 and a monoclonal antibody against CD3 and cultured for 48 hours. Finally, the DC and CIK cells were harvested and suspended in saline for intravenous injection.

Treatment

The patients were randomly divided into the study group (N = 34), which was administered IMRT combined with DC-CIK immunotherapy, and the control group, which was given IMRT only (N = 34).

For IMRT, extracorporeal irradiation was administered using a medical linear accelerator with 6MV X-rays. The gross tumor volume was defined as the gross disease identified in the CT, including the primary esophageal lesion and metastatic lymph nodes. The planning tumor volume was defined as an expansion of the CTV by a 5-8-mm margin, and it was covered by the 95% isodose. Dose fractionation irradiation was used during the procedure for 6-7 weeks with a total dose of 60-66Gy (5 times/ week, 2Gy/session, once/day).

For the patients in the study group, IMRT was administered on day 3 and terminated 2 days before transfusion of the DC and CIK cells. For each session, 200 mL DC and CIK cells containing 1x109CIK cells and 1×107 DC cells were transfused each day for 5 days. Approximately 30 minutes prior to cell transfusion, diphenhydramine (20 mg) was injected intramuscularly.

Results

Side effects
In the study group, the major side effects included shiver and severe fever (N = 3), overexcitation (N = 12), and insomnia due to overexcitation (N = 4). These symptoms were partially or completed relieved after symptomatic treatment. In the control group, the side effects included fever (N = 1) as well as overexcitation and/or insomnia (N = 5). Compared with the control group, only the incidence of overexcitation was significantly different in the study group.
After IMRT and DC-CIK immunotherapy, mild (N = 2) or moderate (N = 2) bone marrow suppression was noted in the study group. Meanwhile, in the control group, severe bone marrow suppression was noted in a number of patients, including degree I (N = 9) and II (N = 6) suppression. Compared with that in the control group, the incidence of bone marrow suppression was remarkably decreased in the study group.
Short-term efficacy
Three months after treatment, a response evaluation of the treatment plan was performed according to the number of lesions in the radiation field, which revealed that CRs occurred in both groups.For the study group, CRs and PRs were noted in 4 (11.8%) and 10 patients (29.4%), respectively. In addition, SD was observed in 15 patients (44.1%), whereas 5 patients (14.7%) displayed PD. In total, the objective response rate was 41.2%, and the disease control rate was 85.3%.
In the control group, CRs and PRs were observed in 3 (8.8%) and 7 patients (20.6%), respectively. In addition, SD was noted in 10 patients (29.4%), whereas 14 patients (41.1%) exhibited PD. The objective response rate was 29.4%, and the disease control rate was 61.7%.
Quality of life
In the study group, 21 patients reported improvements of life quality, and 10 patients exhibited stable health conditions. Nevertheless, deterioration was noticed in 2 patients. On the contrary, 14 patients in the control group reported improvements of life quality, and 8 patients displayed stable health conditions. However, deterioration was noted in 12 patients. Compared with the control group, the overall quality of life was improved in the study group.

Conclusion

In conclusion, DC-CIK therapy plus radiotherapy was safe and effective in treating EC in elderly patients.

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Scientific article publishing date : 2/2/2015

Immucura identifier BSC21_178EN

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