3064 - First Exploration of the Characterization and Dosimetric Predictors for Absolute Lymphocyte Count Changes during nCRT with or without Pembrolizumab for Esophageal Squamous Cell Carcinoma: An Analysis

W. X. Qi^1,2, H. Li³, S. Li², S. Zhao^2,4, and J. Y. Chen²; ¹Shanghai Key Laboratory of Proton-therapy, shanghai, China, ²Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, ³ruijin hospital, shanghai jiaotong university school of medicine, Shanghai, China, ⁴Shanghai Key Laboratory of Proton-therapy, Shanghai, China

Purpose/Objective(s): Whether the addition of pembrolizumab to neoadjuvant chemoradiotherapy (nCRT) for ESCC patients would impact the changes of absolute lymphocyte count (ALC) and treatment response is unknown. The feasibility of lymphocyte-related organs at risk (LOARs)-sparing treatment planning for ESCC is undetermined. Materials/

Methods: A total of 216 ESCC patients who received nCRT (with pembrolizumab 144; without pembrolizumab: 72) were identified from a prospective cohort. Weekly and 1-month post-nCRT ALC were identified. lymphocyte-related organs at risk (LOARs) was delineated. linear and logistic regression analysis was used to analyze the association between G4 lymphopenia/lymphopenia nadir and clinical/DVHs factors.
Results: G4 lymphopenia was observed in 35 ESCC patients (16.2%) during neoadjuvant treatment. The addition of pembrolizumab to nCRT significantly improve lymphopenia recovery at the 1-months after nCRT (p=0.0003), but the ALC at other time point during nCRT and ALC nadir was comparable between the two groups. A total of 188 patients finally received surgery. Of them, 86 patients archived pCR (45.7%), with 47.2% in nCRT with pembrolizumab and 42.6% in nCRT alone(p=0.71). The mean ALC nadir in the pCR group was significantly higher than those without (p=0.035). And patients experiencing grade 4 lymphopenia was associated with poor treatment response to neoadjuvant treatment (TRG 0-1: 51.6% vs. 71.3%, p=0.052), but not for pCR (p=0.90). Multi-variate linear and logistic regression analysis indicated that LOARs were significantly associated with developing G4 lymphopenia(table 1). Dosimetric analysis showed that lymphocyte-sparing photon or proton irradiation was feasible while did not compromise clinically acceptable objectives.
Conclusion: The addition of pembrolizumab to nCRT improve lymphopenia recovery at 1-months after nCRT. ALC nadir and G4 lymphopenia was associated with nCRT response in ESCC patients. Sparing of LOARs using advanced radiation techniques may reduce the risk of developing lymphopenia and improve treatment response in the era of immunotherapy.

Abstract 3064 – Table 1: Multiple Logistic Regression

Variable	OR(95%CI)	SE	AIC	p
Age*	-	-	-	-
BMI*	-	-	-	-
Sex*	-	-	-	-
Tumor length*	-	-	-	-
nCRT regimen*	-	-	-	-
Thoracic TVB
Thoracic vertebrae V40	-	-	-	-
Thoracic vertebrae V30	-	-	-	-
Thoracic vertebrae V20	1.02(0.99-1.04)	0.011	-	0.18
Thoracic vertebrae V10	1.03(1.01-1.06)	0.012	188.8	0.005
Thoracic vertebrae V5	1.03(1.02-1.06)	0.012	185.5	0.0012
Mean thoracic vertebrae dose	1.11(1.03-1.20)	0.038	189.4	0.0069
Mean cardiopulmonary dose	1.32(1.12-1.56)	0.084	185.0	0.00083
Mean whole body dose	1.41(1.04-1.92)	0.16	192.8	0.028
Ribs
V40	-	-		-
V30	-	-		-
V20	-	-		-
V10	-	-		-
V5	1.03(0.99-1.04)	0.012	-	0.15
Mean ribs dose	1.33(1.09-1.63)	0.1	189.9	0.0055
Spleen dose
V40	-	-		-
V30	1.02(0.99-1.04)	0.012	-	0.12
V20	1.02(1.00-1.03)	0.008	192.6	0.017
V10	1.02(1.01-1.03)	0.006	188.9	0.003
V5	1.02(1.01-1.03)	0.006	184.7	0.0045
Mean spleen dose	1.11(1.05-1.18)	0.03	185.6	0.00042