Impact of body dose parameters on circulating immune cells in locally advanced nasopharyngeal carcinoma patients: a retrospective cohort study

doi:10.19401/j.cnki.1007-3639.2023.10.002

Abstract

Abstract:

Background and purpose: The implementation of intensity-modulated radiotherapy (IMRT) has significantly enhanced the survival outcomes for patients with nasopharyngeal carcinoma (NPC). However, this therapeutic approach still falls short in meeting the prognostic requirements of individuals with locally advanced NPC (LANPC). Therefore, it is imperative to identify effective prognostic markers to enhance the efficacy of radiotherapy and achieve personalized treatment. Given the potential predictive value demonstrated in previous studies regarding radiotherapy-related body dose parameters and immune blood cells, this study aimed to investigate the correlation between body dose parameters and reduced immune cells and patient prognosis during radiotherapy in LANPC patients. Methods: Clinical data of 423 patients with LANPC (stage Ⅲ-Ⅳa) treated in Fudan University Shanghai Cancer Center from Jan.1, 2012 to Dec. 31, 2016 were retrospectively analyzed. Percentage changes of different immune blood cells during radiotherapy were also collected. Cox proportional hazard model was used to determine prognostic factors for overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Body dose-based parameters were extracted from dose-volume histograms (DVHs). Logistic regression was applied to determine parameters that could predict white blood cells reduction. Results: High ΔLYM% (ΔLYM%≥7 7.0%) and high ΔMONO% (ΔMONO%≥2 8.5%) were identified as two adverse prognostic factors in LANPC patients. In multivariable analysis, high ΔLYM% was found to be a significant predictor of worse OS (HR = 1.672, P = 0.012), LRFS (HR = 1.712, P = 0.006), and DMFS (HR = 1.971, P = 0.001). High ΔMONO% was associated with worse OS (HR = 1.355, P = 0.015) and DMFS (HR = 1.704, P = 0.003). The change of ΔLYM% was influenced by the integral body dose (IBD) (OR = 1.004, P = 0.037) and body V₆₀ (OR = 1.046, P = 0.036). ΔMONO% was significantly affected by body V₅₅ (OR = 1.144, P = 0.009) and V₇₀ (OR = 0.734, P = 0.022). Conclusion: Integral body dose, V₆₀, and V₅₅, V₇₀ can serve as dose-volume constraints to retain sufficient immune cell populations to improve prognosis.

Key words: Cohort study, Retrospective study, Locally advanced nasopharyngeal carcinoma, Lymphocyte, Monocyte, Body dose parameter

CLC Number:

JIANG Jianyun, ZHAI Ruiping, YING Hongmei. Impact of body dose parameters on circulating immune cells in locally advanced nasopharyngeal carcinoma patients: a retrospective cohort study[J]. China Oncology, 2023, 33(10): 898-907.

Figures/Tables 6

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Characteristics	Overall (n = 423)	Characteristics	Overall (n = 423)
Gender n (%)		Concurrent chemotherapy n (%)
Female	110 (26.0)	Yes	104 (24.6)
Male	313 (74.0)	No	319 (75.4)
Age, median (IQR)	49 (40, 57)	Adjuvant chemotherapy n (%)
Overall stage n (%)		Yes	179 (42.3)
Ⅲ	168 (39.7)	No	244 (57.7)
ⅣA	255 (60.3)	Dose to PTV-G (Gy) n (%)
T stage		66.0	88 (20.8)
T₁	23 (5.4)	70.4	335 (79.2)
T₂	113 (26.7)	ΔWBC n (%)
T₃	176 (41.6)	<25.5%	211 (49.9)
T₄	111 (26.2)	≥25.5%	212 (50.1)
N stage		ΔLYM n (%)
N₀	6 (1.4)	<77.0%	206 (48.7)
N₁	76 (18.0)	≥77.0%	217 (51.3)
N₂	169 (40.0)	ΔMONO n (%)
N₃	172 (40.7)	<28.5%	211 (49.9)
Pathological type n (%)		≥28.5%	212 (50.1)
Non-keratinized differentiated	10 (2.4)	ΔNEU n (%)
Non-keratinized undifferentiated	413 (97.6)	<22.6%	211 (49.9)
Induction chemotherapy n (%)		≥22.6%	212 (50.1)
Yes	286 (67.6)	ΔPLT n (%)
No	137 (32.4)	17.0%	211 (49.9)
		≥17.0%	212 (50.1)

Characteristics	OS		LRFS		DMFS
Characteristics	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Gender (male vs female) (male vs female)	-	-	-	-	1.81 (0.92-3.58)	0.087
Age	1.05 (1.02-1.07)	<0.001	1.02 (0.99-1.04)	0.144	-	-
TNM Ⅳa vs TMN Ⅲ (ⅣA vs Ⅲ)	3.08 (1.72-5.51)	<0.001	2.61 (1.32-5.17)	0.006	2.06 (1.56-4.40)	0.023
Induction chemotherapy	0.26 (0.15-0.46)	<0.001	0.39 (0.24-0.64)	<0.001	0.25 (0.15-0.41)	< 0.001
Concurrent chemotherapy	-	-	-	-	-	-
Adjuvant chemotherapy	0.50 (0.27-0.93)	0.028	-	-	-	-
PTV-G (70.4 vs 60.0 Gy)	-	-	-	-	-	-
ΔWBC%	-	-	-	-	-	-
ΔLYM%	1.18 (1.02-2.32)	0.043	1.13 (1.08-1.64)	0.028	1.31 (1.09-2.50)	0.011
ΔMONO%	1.03 (1.01-2.01)	0.047	-	-	1.17 (1.02-2.07)	0.021
ΔNEU%	-	-	1.60 (0.99-2.59)	0.055	-	-
ΔPLT%	-	-	-	-	-	-

Characteristics	Univariable analysis		Multivariable analysis
Characteristics	Odds ratio (95% CI)	P value	Odds ratio (95% CI)	P value
Gender
Female	Reference
Male	0.925 (0.587-1.458)	0.738	-	-
Age	1.070 (1.054-1.086)	<0.001	1.071 (1.054-1.087)	<0.001
Overall stage
Ⅲ	Reference
ⅣA	1.171 (0.778-1.761)	0.449	-	-
Induction chemotherapy
No	Reference
Yes	1.290 (0.838-1.984)	0.247	-	-
Concurrent chemotherapy
No	Reference
Yes	1.471 (0.925-2.339)	0.103	-	-
PTV-P
66.0	Reference
70.4	1.066 (0.629-1.806)	0.812	-	-
MBD	1.000 (1.000-1.000)	0.129	-	-
IBD	1.004 (1.001-1.009)	0.013	1.004 (1.001-1.010)	0.037
V₅	1.002 (0.970-1.009)	0.321	-	-
V₁₅	1.018 (0.967-1.111)	0.317	-	-
V₄₅	1.019 (0.964-1.078)	0.501	-	-
V₅₅	1.000 (0.937-1.067)	0.989	-	-
V₆₀	1.068 (1.006-1.169)	0.053	1.046 (1.030-1.154)	0.036
V₆₅	1.003 (0.892-1.105)	0.892	-	-
V₇₀	0.946 (0.765-1.171)	0.612	-	-

Characteristics	Univariable analysis		Multivariable analysis
Characteristics	Odds ratio (95% CI)	P value	Odds ratio (95% CI)	P value
Gender
Female	Reference
Male	0.881 (0.540-1.439)	0.612	-	-
Age	0.993 (0.976-1.010)	0.399	-	-
Overall stage
Ⅲ	Reference		Reference
ⅣA	0.668 (0.429-1.041)	0.075	0.512 (0.275-0.954)	0.035
Induction chemotherapy
No	Reference
Yes	0.899 (0.567-1.427)	0.653	-	-
Concurrent chemotherapy
No	Reference
Yes	1.386 (0.835-2.299)	0.207	-	-
PTV-P
66.0	Reference
70.4	1.082 (0.614-1.907)	0.786	-	-
MBD	1.000 (1.000-1.001)	0.224	-	-
IBD	0.997 (0.991-1.002)	0.228	-	-
V₅	1.010 (0.990-1.032)	0.327	-	-
V₅₅	1.068 (0.988-1.154)	0.097	1.144 (1.034-1.265)	0.009
V₇₀	0.827 (0.661-1.034)	0.096	0.734 (0.564-0.957)	0.022