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. 2024 May 23;65(3):337-349.
doi: 10.1093/jrr/rrae023.

The relationship between splenic dose and radiation-induced lymphopenia

Yifu Ma  1   2   3 , Yuehong Kong  1   2   3 , Shuying Zhang  4 , Yong Peng  1   2   3 , Meiling Xu  1   2   3 , Junjun Zhang  1   2   3 , Hong Xu  1   5 , Zhihui Hong  6 , Pengfei Xing  1   2   3 , Jianjun Qian  1   2   3 , Liyuan Zhang  1   2   3   7
Affiliations

The relationship between splenic dose and radiation-induced lymphopenia

Yifu Ma et al. J Radiat Res. .

Abstract

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.

Keywords: dose constraints for the spleen; lymphopenia; radiotherapy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flow diagram of patient selection according to the eligibility criteria and exclusion criteria.
Figure 2
Figure 2
The kinetics of lymphocyte counts during radiotherapy. The median values (×109 cells/L) of pre-treatment ALC, min ALC and post-treatment ALC are 1.40 (range, 0.30–3.10), 0.23 (range, 0.04–1.66) and 0.28 (range, 0.04–2.76), respectively.
Figure 3
Figure 3
ALC trend of 96 gastric cancer patients who received postoperative CRT.
Figure 4
Figure 4
Kaplan–Meier estimate of OS and DFS.
Figure 5
Figure 5
Overall survival with ΔALC dichotomized by median. ΔALC = the difference between pre-treatment ALC and minimum ALC during radiotherapy.
Figure 6
Figure 6
Overall survival with NLR dichotomized by median.
Figure 7
Figure 7
Kaplan–Meier curves show OS (A and C), DFS (B and D) of gastric cancer patients, grouped by lymphopenia grade (Common Terminology Criteria for Adverse Events 5.0) based on ALC post CRT.
See this image and copyright information in PMC

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