Acute severe lymphopenia by radiotherapy is associated with reduced overall survival in hepatocellular carcinoma

  • Hwa Kyung Byun
  • Nalee Kim
  • Sangjoon Park
  • Jinsil SeongEmail author
Original Article



Radiotherapy (RT) for peripheral organs can affect circulating lymphocytes and cause lymphopenia. We aimed to investigate RT-related lymphopenia in patients with hepatocellular carcinoma (HCC).


Medical records of 920 patients who received RT for HCC during 2001–2016 were reviewed. Total lymphocyte count (TLC) were obtained and analyzed for clinical outcome. Acute severe lymphopenia (ASL) was defined as TLC <500/μL within the first 3 months of the start of RT.


The median TLCs before and 1 month after the start of RT were 1120 and 310/μl, respectively, and the TLCs did not recover to their initial level after 1 year. Overall, 87.4% of patients developed ASL. The median overall survival was 13.6 and 46.7 months for patients with and without ASL, respectively (p < 0.001). ASL was independently associated with poor overall survival with a hazard ratio (HR) of 1.40; 95% confidence interval (CI), 1.02–1.91 (p = 0.035). In the multivariate analysis, larger planning target volume (HR, 1.02; 95% CI, 1.01–1.03; p < 0.001) and lower baseline TLC (HR, 0.86; 95% CI, 0.82–0.91; p < 0.001) were significantly associated with an increased risk of ASL, while hypofractionation (stereotactic body RT: HR, 0.19; 95% CI, 0.07–0.49; p = 0.001) was significantly associated with a reduced risk of ASL.


Acute severe lymphopenia after RT was associated with poor overall survival in patients with HCC. Stereotactic body RT may reduce the risk of ASL. Further attention to and research on the cause, prevention, and reversal of this phenomenon are needed.


Liver cancer Total lymphocyte count Hypofractionation Planning target volume Immunotherapy 

Akute schwere Lymphopenie durch Strahlentherapie ist beim hepatozellulären Karzinom mit reduziertem Gesamtüberleben assoziiert



Strahlentherapie (RT) für Peripherieorgane kann zirkulierende Lymphozyten schädigen und Lymphopenie verursachen. Wir haben zum Ziel, RT-bezogene Lymphopenie bei Patienten mit Leberkarzinom zu erforschen (HCC).


Überprüft wurden medizinische Aufzeichnungen von 920 Patienten, die in den Jahren 2001–2016 eine Strahlentherapie bei HCC erhalten hatten. Die Gesamtanzahl der Lymphozyten (TLC) wurde bestimmt und für klinische Ergebnisse analysiert. Akute schwere Lymphopenie (ASL) wurde als TLC <500/μl innerhalb der ersten 3 Monate nach Beginn der RT definiert.


Der Mittelwert der TLC vor und 1 Monat nach Beginn der RT lag bei jeweils 1120 und 310/μl, und die TLC erreichte auch nach 1 Jahr nicht ihr Ursprungsniveau. Insgesamt entwickelten 87,4% der Patienten eine ASL. Die mittlere Gesamtüberlebensrate lag jeweils bei 13,6 und 46,7 Monaten bei Patienten mit und ohne ASL (p < 0,001). ASL wurde unabhängig mit schlechter Überlebensrate in Verbindung gesetzt (Hazard Ratio [HR] 1,40; 95%-Konfidenzintervall [KI] 1,02–1,91; p = 0,035). In der mehrdimensionalen Analyse wurden geplante Zielmenge (HR 1,02; 95%-KI 1,01–1,03; p < 0,001) und geringere TLC-Basislinie (HR 0,86; 95%-KI 0,82–0,91; p < 0,001) maßgeblich mit einem erhöhten Risiko von ASL in Verbindung gesetzt, während Hypofraktionierung (stereotaktische Körper-RT: HR 0,19; 95%-KI 0,07–0,49; p = 0,001) mit einem reduzierten Risiko von ASL in Verbindung gesetzt wird.


ASL nach RT wurde mit schlechter allgemeiner Überlebensrate bei Patienten mit HCC in Verbindung gebracht. Stereotaktische Körper-RT kann das Risiko von ASL reduzieren. Zusätzliche Aufmerksamkeit und Ursachenforschung, Verhütung und Umkehr dieses Phänomens werden benötigt.


Leberkrebs Gesamtanzahl der Lymphozyten Hypofraktionierung Geplante Zielmenge Immuntherapie 



This study was supported by National Nuclear R&D Program through a National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Grant number; 2017070426)

Compliance with ethical guidelines

Conflict of interest

H.K. Byun, N. Kim, S. Park and J. Seong declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

66_2019_1462_MOESM1_ESM.tif (5 mb)
Supplementary Fig. 1 The probability of ASL in relation to increasing PTV size


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation Oncology, Yonsei Cancer CenterYonsei University College of MedicineSeodaemun-gu, SeoulKorea (Republic of)

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