Treatment-Related Lymphopenia Predicts Pathologic Complete Response and Recurrence in Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy

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To investigate the relationship between treatment-related lymphopenia and pathologic response to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).


Between 2002 and 2016, 220 ESCC patients treated with neoadjuvant CRT followed by surgery were retrospectively analyzed. Absolute lymphocyte count was determined before, during, and 1 month after neoadjuvant CRT. Treatment-related lymphopenia was graded using Common Terminology Criteria for Adverse Events version 4.0. Relationship between lymphopenia with pathologic complete response (pCR) and recurrence were evaluated.


Ninety-five patients (43.2%) achieved a pCR after neoadjuvant CRT and 71 patients (32.3%) developed recurrences. The incidence of grade 0, 1, 2, 3, and 4 lymphopenia during CRT were 1.8%, 6.8%, 31.4%, 38.2% and 21.8%, respectively. Patients with grade 4 lymphopenia had a significantly lower pCR rate than those with grade 0-3 lymphopenia (22.9% vs. 48.8%, P = 0.001). Moreover, grade 4 lymphopenia was significantly associated with a higher risk of recurrences (45.8% vs. 28.5%, P = 0.023). Multivariable analysis identified that primary tumor length, tumor location, and radiation dose were independent predictors for grade 4 lymphopenia.


ESCC patients with grade 4 lymphopenia during neoadjuvant CRT were associated with a significantly lower pCR rate and a higher recurrence risk.

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This work was supported by Grants from the National Natural Science Foundation of China (No. 81874220) and Guangdong Esophageal Cancer Institute Science and Technology Program (M201715).

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Correspondence to Yonghong Hu MD or Mian Xi MD.

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Li, Q., Zhou, S., Liu, S. et al. Treatment-Related Lymphopenia Predicts Pathologic Complete Response and Recurrence in Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy. Ann Surg Oncol 26, 2882–2889 (2019).

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