Clinical significance of circulating cytokine profiles in predicting radioactive pulmonary fibrosis in patients with non-small cell lung cancer

doi:10.3877/cma.j.issn.1674-6902.2025.04.019

Abstract

Abstract:

Objective

To analyze the clinical significance of circulating cytokine profiling in predicting radiation-induced pulmonary fibrosis (RILF) in patients with non-small cell lung cancer (NSCLC).

Methods

A total of 86 patients with stage Ⅰ-Ⅲ NSCLC who underwent radical thoracic radiotherapy in the First Affiliated Hospital of Xi'an Jiaotong University Yulin Hospital from January 2021 to December 2024 were selected and divided into a training set of 63 cases and a validation set of 23 cases in a ratio of 7︰3. The clinical data of the patients were collected. Circulating cytokines were detected by the human cytokine/chemotactic magnetic bead panel kit and the enzyme-linked immunosorbent assay kit. The occurrence of RILF≥ grade 2 (RILF2) in the patients was recorded.

Results

There were 11 cases (17.46%) of RILF2 in the training set and 4 cases (17.39%) of RILF2 in the validation set (χ²=0.001, P=0.994). The median onset time of RILF2 in patients was 4.90 months. Logistic and LASSO regression analyses showed that the mean lung dose(MLD) (HR: 3.674, 95%CI: 1.240~10.887), interleukin-8 (IL-8) (HR: 0.231, 95%CI: 0.060~0.887), C-C chemokine ligand 4 (CCL4) (HR: 0.204, 95%CI: 0.053~0.777), transforming growth factor-β1 (TGF-β1) (HR: 21.831, 95%CI: 1.609~296.240) are the influencing factors of RILF2 in NSCLC patients. The nomogram predicted the RILF2 of the training set and the validation set, and the area under the receiver operating characteristic curve was 0.884 (95%CI: 0.779~0.989) and 0.841 (95%CI: 0.672~0.990), respectively. The Hosmer-Lemeshow test results showed a good fit (P>0.05), and the high-risk thresholds were 0.05-0.73 and 0.09-0.68, respectively.

Conclusion

The nomogram of cytokines MLD, IL-8, CCL4, TGF-β1 and the dosimetric factor RILF2 has clinical significance in predicting RILF in NSCLC patients.

Key words: Non-small cell lung cancer, Circulating cytokines, Radiation-induced lung fibrosis, Nomogram

Junxia Wu, Gang Huo, Jiaojiao Li, Huihui Yang, Ming Ma, Wangfeng Zhang. Clinical significance of circulating cytokine profiles in predicting radioactive pulmonary fibrosis in patients with non-small cell lung cancer[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 603-608.

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References 30

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临床资料	训练集(n＝63)	验证集(n＝23)	Z/t/χ²	P值
吸烟史[n(%)]			0.207	0.902
从未吸烟	7(11.11)	3(13.04)
既往吸烟	28(44.44)	9(39.13)
吸烟	28(44.44)	11(40.74)
KPS[分，(±s)]	84.13±9.44	81.48±9.49	1.218	0.226
化疗[n(%)]	46(73.02)	19(82.61)	0.840	0.359
组织学亚型[n(%)]			0.249	0.618
鳞状细胞癌	42(66.67)	14(60.87)
非鳞状细胞癌	21(33.33)	9(39.13)
临床分期[n(%)]			0.236	0.889
Ⅰ期	11(17.46)	5(18.52)
Ⅱ期	5(7.94)	2(7.41)
Ⅲ期	47(74.60)	16(69.57)
T分期[n(%)]			2.546	0.467
T1	12(19.05)	6(22.22)
T2	13(20.63)	7(25.93)
T3	17(26.98)	3(13.04)
T4	21(33.33)	7(25.93)
N分期[n(%)]			3.981	0.264
N0	18(28.57)	4(17.39)
N1	5(7.94)	2(7.41)
N2	30(47.62)	9(39.13)
N3	10(15.87)	8(29.63)
GTV[cm³，M₅₀(P₂₅，P₇₅)]	139.29(53.16，294.36)	100.10(37.04，221.97)	－1.290	0.197
总辐射剂量[Gy，(±s)]	67.77±7.36	69.96±6.89	1.318	0.191
MLD[Gy，M₅₀(P₂₅，P₇₅)]	14.46(11.91，17.23)	14.99(12.43，17.55)	－0.392	0.695
V20[%，M₅₀(P₂₅，P₇₅)]	24.09(17.51，29.81)	25.42(22.07，29.33)	－0.691	0.489

临床资料	训练集(n＝63)	验证集(n＝23)	Z/t/χ²	P值
吸烟史[n(%)]			0.207	0.902
从未吸烟	7(11.11)	3(13.04)
既往吸烟	28(44.44)	9(39.13)
吸烟	28(44.44)	11(40.74)
KPS[分，(±s)]	84.13±9.44	81.48±9.49	1.218	0.226
化疗[n(%)]	46(73.02)	19(82.61)	0.840	0.359
组织学亚型[n(%)]			0.249	0.618
鳞状细胞癌	42(66.67)	14(60.87)
非鳞状细胞癌	21(33.33)	9(39.13)
临床分期[n(%)]			0.236	0.889
Ⅰ期	11(17.46)	5(18.52)
Ⅱ期	5(7.94)	2(7.41)
Ⅲ期	47(74.60)	16(69.57)
T分期[n(%)]			2.546	0.467
T1	12(19.05)	6(22.22)
T2	13(20.63)	7(25.93)
T3	17(26.98)	3(13.04)
T4	21(33.33)	7(25.93)
N分期[n(%)]			3.981	0.264
N0	18(28.57)	4(17.39)
N1	5(7.94)	2(7.41)
N2	30(47.62)	9(39.13)
N3	10(15.87)	8(29.63)
GTV[cm³，M₅₀(P₂₅，P₇₅)]	139.29(53.16，294.36)	100.10(37.04，221.97)	－1.290	0.197
总辐射剂量[Gy，(±s)]	67.77±7.36	69.96±6.89	1.318	0.191
MLD[Gy，M₅₀(P₂₅，P₇₅)]	14.46(11.91，17.23)	14.99(12.43，17.55)	－0.392	0.695
V20[%，M₅₀(P₂₅，P₇₅)]	24.09(17.51，29.81)	25.42(22.07，29.33)	－0.691	0.489

影响因素	β	SE	Walds值	HR(95%CI)	P值
年龄(0＝<60岁，1＝≥60岁)	0.015	0.035	0.190	1.015(0.948~1.087)	0.663
性别(0＝女，1＝男)	－0.201	0.871	0.053	0.818(0.148~4.512)	0.818
吸烟史(0＝从未吸烟，1＝既往吸烟/吸烟)	0.636	0.556	1.310	1.890(0.636~5.617)	0.252
KPS(0＝<90分，1＝≥90分)	0.006	0.036	0.027	1.006(0.937~1.080)	0.870
化疗(0＝否，1＝是)	0.601	0.840	0.513	1.824(0.352~9.456)	0.474
组织学亚型(0＝鳞状细胞癌，1＝非鳞状细胞癌)	－0.491	1.206	0.166	0.612(0.058~6.505)	0.684
临床分期(0＝Ⅰ，1＝Ⅱ/Ⅲ)	0.667	0.600	1.237	1.949(0.601~6.314)	0.266
T分期(0＝T1/T2，1＝T3/T4)	0.471	0.337	1.949	1.602(0.827~3.103)	0.163
N分期(0＝N0/N1，1＝N2/N3)	0.352	0.336	1.097	1.422(0.736~2.749)	0.295
GTV(0＝<139.29 cm³，1＝≥139.29 cm³)	0.001	0.002	0.530	1.001(0.998~1.005)	0.467
总辐射剂量(0＝<67.80 Gy，1＝≥67.80 Gy)	0.020	0.046	0.185	1.020(0.932~1.116)	0.667
MLD(0＝<14.46 Gy，1＝≥14.46 Gy)	0.750	0.231	10.553	2.116(1.346~3.327)	0.000
V20(0＝<24.09%，1＝≥24.09%)	0.105	0.051	4.193	1.111(1.005~1.228)	0.041
IL-8(0＝<2.50，1＝≥2.50)	－0.817	0.330	6.142	0.442(0.231~0.843)	0.013
CCL4(0＝<3.90，1＝≥3.90)	－0.853	0.267	10.211	0.426(0.253~0.719)	0.001
TGF-β1(0＝<1.70，1＝≥1.70)	1.931	0.610	10.036	6.898(2.088~22.781)	0.002

影响因素	β	SE	Walds值	HR(95%CI)	P值
年龄(0＝<60岁，1＝≥60岁)	0.015	0.035	0.190	1.015(0.948~1.087)	0.663
性别(0＝女，1＝男)	－0.201	0.871	0.053	0.818(0.148~4.512)	0.818
吸烟史(0＝从未吸烟，1＝既往吸烟/吸烟)	0.636	0.556	1.310	1.890(0.636~5.617)	0.252
KPS(0＝<90分，1＝≥90分)	0.006	0.036	0.027	1.006(0.937~1.080)	0.870
化疗(0＝否，1＝是)	0.601	0.840	0.513	1.824(0.352~9.456)	0.474
组织学亚型(0＝鳞状细胞癌，1＝非鳞状细胞癌)	－0.491	1.206	0.166	0.612(0.058~6.505)	0.684
临床分期(0＝Ⅰ，1＝Ⅱ/Ⅲ)	0.667	0.600	1.237	1.949(0.601~6.314)	0.266
T分期(0＝T1/T2，1＝T3/T4)	0.471	0.337	1.949	1.602(0.827~3.103)	0.163
N分期(0＝N0/N1，1＝N2/N3)	0.352	0.336	1.097	1.422(0.736~2.749)	0.295
GTV(0＝<139.29 cm³，1＝≥139.29 cm³)	0.001	0.002	0.530	1.001(0.998~1.005)	0.467
总辐射剂量(0＝<67.80 Gy，1＝≥67.80 Gy)	0.020	0.046	0.185	1.020(0.932~1.116)	0.667
MLD(0＝<14.46 Gy，1＝≥14.46 Gy)	0.750	0.231	10.553	2.116(1.346~3.327)	0.000
V20(0＝<24.09%，1＝≥24.09%)	0.105	0.051	4.193	1.111(1.005~1.228)	0.041
IL-8(0＝<2.50，1＝≥2.50)	－0.817	0.330	6.142	0.442(0.231~0.843)	0.013
CCL4(0＝<3.90，1＝≥3.90)	－0.853	0.267	10.211	0.426(0.253~0.719)	0.001
TGF-β1(0＝<1.70，1＝≥1.70)	1.931	0.610	10.036	6.898(2.088~22.781)	0.002

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