Severance Hospital, Yonsei Cancer Center, Seodaemungu, South Korea
Yong Tae Kim , Byung Min Lee , Jinsil Seong
Background: Promising therapeutic results of immune checkpoint inhibitor (ICI) have been reported in various solid tumors. Radiotherapy (RT) is known to enhance the immunogenic effect. The immunogenic effect of RT is expected to improve the therapeutic effect of ICI. In this study, we aimed to investigate the efficacy and toxicity of combining ICI and RT in hepatobiliary cancer. Methods: Patients who received RT and ICI combination therapy for hepatobiliary cancer from January 2020 to April 2021 were retrospectively reviewed. Baseline patient characteristics such as age at diagnosis, stage, previous treatment, radiation dose, tumor volume, and lymphocyte count were recorded. The primary endpoints were in-field and out-field control rate. The secondary endpoint was treatment-related toxicities. Overall survival and progression-free survival were also evaluated. The disease control rate and survival were assessed using the Kaplan-Meier method. Results: In total, 17 patients and 35 treated lesions were included for analysis. The median follow up period was 5.5 months (range 2.4 – 19.8 months). Of the 17 patients, 14 were diagnosed hepatocellular carcinoma (82.4%). Twelve patients had distant metastasis (70.6%). Various treatments were administered to the patients prior to ICI and RT combination treatment. The 6-month overall survival and progression-free survival was 62.7% and 26.5%, respectively. The 6-month in-field control rate was 67.4% and 6-month out-field control rate was 26.6%. Higher BED (≥ 90 Gy) was a significant prognostic factor for both in-field and out-field control, and lymphopenia (≤ 800 /μL) at the time of RT start was a poor prognostic factor for outfield control. Fractional dose of less than 5 Gy showed improved in-field and out-field control. Treatment related toxicity occurred in 10 patients (58.8%). The most frequent adverse event was GI disorders such as esophagitis (n = 3) and epigastric pain (n = 3). Patients who experienced treatment-related toxicity were well recovered after conservative care. There was no grade 3 or 4 toxicity. Conclusions: The combination of ICI and RT showed substantial efficacy with acceptable toxicity in heavily pretreated advanced hepatobiliary cancer patients. Dose per fraction of less than 5 Gy may be appropriate for better efficacy in future study of combining ICI and RT. The results of this study provides a basis for future prospective study in hepatobiliary cancer.
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