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. 2023 Aug 3;28(8):e645-e652.
doi: 10.1093/oncolo/oyad109.

Less Irradiation to Lymphocyte-Related Organs Reduced the Risk of G4 Lymphopenia in Esophageal Cancer: Re-Analysis of Prospective Trials

Ihsuan Tseng  1   2   3   4 , Fangfang Li  5 , Dashan Ai  1   2   3   4 , Yun Chen  1   2   3   4 , Yang Xu  6 , Lu Yu  7 , Shengnan Hao  1   2   3   4 , Hongcheng Zhu  1   2   3   4 , Jiaying Deng  1   2   3   4 , Qi Liu  1   2   3   4 , Fan Pan  5 , Fengtao Su  1   4 , Kuaile Zhao  1   2   3   4
Affiliations

Less Irradiation to Lymphocyte-Related Organs Reduced the Risk of G4 Lymphopenia in Esophageal Cancer: Re-Analysis of Prospective Trials

Ihsuan Tseng et al. Oncologist. .

Abstract

Background: This study aimed to explore the relationship between irradiation of lymphocyte-related organs at risk (LOARs) and lymphopenia during definitive concurrent chemoradiotherapy (dCCRT) for esophageal squamous cell carcinoma (ESCC).

Materials and methods: Cases of ESCC patients who received dCCRT from 2 prospective clinical trials were identified. To find its correlation with survival outcomes, grades of absolute lymphocyte counts (ALCs) nadir during radiotherapy were recorded following COX analysis. Associations of lymphocytes at nadir and dosimetric parameters including relative volumes of spleen and bone marrow receiving 0.5, 1, 2, 3, 5, 10, 20, 30, and 50Gy (V0.5, V1, V2, V3, V5, V10, V20, V30, and V50), and effective dose to circulating immune cells (EDIC) were examined by logistic risk regression analysis. The cutoffs of dosimetric parameters were determined by the receiver operating characteristic curve (ROC).

Results: A total of 556 patients were included. The incidences of grades 0, 1, 2, 3, and 4 (G4) lymphopenia during dCCRT were 0.2%, 0.5%, 9.7%, 59.7%, and 29.8%, respectively. Their median overall survival (OS) and progression-free survival (PFS) time were 50.2 and 24.3 months, respectively; the incidence of local recurrence and distant metastasis were 36.6% and 31.8%, respectively. Patients once suffering from G4 nadir during radiotherapy had unfavorable OS (HR, 1.28; P = .044) and a higher incidence of distant metastasis (HR, 1.52; P = .013). Furthermore, patients with EDIC ≤8.3Gy plus spleen V0.5 ≤11.1% and bone marrow V10 ≤33.2% were strongly associated with lower risk of G4 nadir (OR, 0.41; P = .004), better OS (HR, 0.71; P = .011) and lower risk of distant metastasis (HR, 0.56; P = .002).

Conclusions: Smaller relative volumes of spleen V0.5 and bone marrow V10 plus lower EDIC were jointly prone to reduce the incidence of G4 nadir during definitive concurrent chemoradiotherapy. This modified therapeutic strategy could be a significant prognostic factor for survival outcomes in ESCC.

Keywords: chemoradiotherapy; esophageal cancer; lymphocyte-related organs at risk.

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Conflict of interest statement

The authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Screening strategy for inclusion in the study. Four hundred thirty-six patients from ESO-Shanghai 1 trial and 321 patients from ESO-Shanghai 2 trial were assessed for eligibility. After the exclusions of patients (1) from other hospitals (n = 160); (2) absent with baseline blood routine (n = 8); (3) with <3 times blood routine during treatment (n = 4); (4) who suspended radiotherapy >1 month (n = 6); (5) without available dosimetric parameters (n = 11); (6) receiving actual dose < 50.4 Gy (n = 12), 556 patients were finally enrolled for the following analyses.
Figure 2.
Figure 2.
Correlations between lymphocytes at nadir and EDIC , dosimetric parameters of the spleen, and bone marrow by Spearman analysis. Abbreviation: EDIC, effective dose of immune cells.
Figure 3.
Figure 3.
Grade 4 nadir cumulative incidence in different groups during dCCRT. “All lower” group : patients with EDIC ≤8.3 Gy, spleen V0.5 ≤11.1%, and bone marrow V10 ≤33.2% at the same time. “All higher” group: patients with EDIC >8.3Gy, spleen V0.5 >11.1%, and bone marrow V10 >33.2% at the same time. Remaining patients were sorted into “others”. The comparisons of G4 nadir and G0-3 lymphopenia distributions were performed between “all lower” group vs. “all higher” group and “others” group. ***Represents P < .001 as analyzed through chi-square test.
Figure 4.
Figure 4.
Kaplan-Meier curves show different clinical outcomes between “all lower” group vs. others + all higher group: (A) overall survival and (B) distant-metastasis (DM). “All lower” group contained patients who received EDIC ≤8.3 Gy along with spleen V0.5 ≤ 11.1% and bone marrow V10 ≤ 33.2%. “All higher” group included patients who received EDIC > 8.3Gy along with spleen V0.5 > 11.1% and bone marrow V10 > 33.2%. The remaining patients were sorted into “others” group.
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