P1.120. AUC-Based Assessment of Lymphocyte Depletion: Chemotherapy Alone Versus Chemoradiotherapy, and Mediastinal Versus Pelvic Chemoradiotherapy Regimens

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ID: 326053
2026
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Abstract
Abstract Topic Esophageal Cancer: Oncology/Radiation Therapy Background Radiotherapy is frequently associated with lymphocyte depletion, which may compromise antitumor immunity and potentially reduce the efficacy of immune checkpoint inhibitors (ICIs). Whether lymphocyte depletion differs by irradiation field remains unclear, particularly under concurrent chemoradiotherapy. Methods We retrospectively analyzed treatment-naïve esophageal cancer patients treated between 2021 and 2024 with either fluorouracil plus cisplatin chemotherapy alone (FP) or concurrent chemoradiotherapy (FP + RT). To explore field-related differences under concurrent chemotherapy, patients with gynecologic malignancies who underwent pelvic radiotherapy with concurrent weekly cisplatin (wCDDP + RT) during the same period were included. Lymphocyte depletion was quantified using an area under the curve (AUC) metric of proportional lymphocyte reduction normalized to baseline absolute lymphocyte count, capturing both magnitude and duration; only reductions below baseline contributed to AUC. AUCs were calculated over 0–50 days (FP vs FP + RT) and over 0–60 and 0–120 days (FP + RT vs wCDDP + RT), with endpoint correction by linear interpolation at window boundaries. Log10-transformed AUC values were compared using a univariate general linear model including age and pretreatment serum albumin as covariates. Bootstrap resampling (5,000 iterations) was used to estimate 95% confidence intervals. Results Compared with FP alone, FP + RT was associated with significantly greater lymphocyte depletion over 0–50 days (F = 30.2, p < 0.001). The FP group showed a lower log10(AUC) than the FP + RT group (B = −0.501, p < 0.001), corresponding to approximately 70% lower AUC after back-transformation. In contrast, no significant difference in lymphocyte depletion was observed between mediastinal FP + RT and pelvic wCDDP + RT over 0–60 days (F = 2.372, p = 0.135; B = −0.104) or 0–120 days (F = 0.543, p = 0.178; B = −0.129), although the mediastinal FP + RT group tended to show lower AUC. Conclusion Adding radiotherapy to FP chemotherapy substantially increased lymphocyte depletion. However, as a treatment package, mediastinal FP-based chemoradiotherapy did not produce significantly greater lymphocyte depletion than pelvic chemoradiotherapy with weekly cisplatin. These findings suggest that clinically meaningful lymphocyte depletion may occur with chemoradiotherapy even outside the mediastinum, underscoring the need to consider lymphocyte preservation when integrating radiotherapy with ICIs.
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Authors Nobukazu Hokamura, Kenshiro Shiraishi, Kazunori Nagasaka, Takashi Mitsui, Kiyoshi Kiyokawa, Masahiro Horikawa, Yuichi Igarashi, Hironori Midorikawa, Shinya Kaneshiro, Kakeo Fukagawa
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Journal diseases of the esophagus : official journal of the international society for diseases of the esophagus
Year 2026
DOI
10.1093/dote/doag077.268
URL
https://doi.org/10.1093/dote/doag077.268
Keywords Keywords not found

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