Analysis on the incidence and risk factors of pneumonia in patients with lung cancer receiving thoracic radiotherapy and immunotherapy

Abstract

Abstract:

ObjectiveTo analyze the incidence, risk factors and occurrence time of radiation pneumonia （RP） and immune checkpoint inhibitor-related pneumonia （CIP） in patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy.MethodsThe clinicopathological data of 137 patients with lung cancer and lung metastatic cancer receiving thoracic radiotherapy and at least one cycle of immunotherapy from January 2019 to January 2022 in Renmin Hospital of Wuhan University were retrospectively analyzed. The occurrence of RP and CIP was determined according to the clinical symptoms and thin-slice chest CT. The risk factors of symptomatic RP were evaluated by univariate and multivariate analyses of clinical data and treatment plan. The relationship between the occurrence time of symptomatic RP and the sequence of thoracic radiotherapy and immunotherapy was compared.ResultsIn the 137 patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy, symptomatic RP was observed in 42 patients （30.7%）, including grade 2 RP in 33 patients （24.1%）, grade 3 RP in 6 patients （4.4%）, grade 4 RP in 1 patient （0.7%）, and grade 5 RP in 2 patients （1.5%）. The incidence of symptomatic RP was 40.0% （28/70） in patients who received thoracic radiation concurrent with immunotherapy and 20.9% （14/67） in non-synchronous patients, and the incidence of severe RP was 10.0% （7/70） and 3.0% （2/67） respectively. CIP was observed in 11 （8.0%） of 137 patients, including grade 2 CIP in 4 patients （2.9%）, grade 3 CIP in 6 patients （4.4%）, grade 5 CIP in 1 patient （0.7%）. There were 54.5% （6/11） of CIP patients with prior or concurrent symptomatic RP. Univariate analysis showed that smoking history （χ²=9.85,P=0.002）, chronic obstructive pulmonary disease （COPD） history （χ²=31.34,P<0.001）, thoracic radiotherapy concurrent with immunotherapy （χ²=5.88,P=0.015）, total radiotherapy dose （χ²=8.57,P=0.003） were associated with symptomatic RP. Multivariate logistic regression analysis showed that COPD history （OR=9.96, 95%CI: 3.40-29.14,P<0.001）, thoracic radiotherapy concurrent with immunotherapy （OR=2.84, 95%CI: 1.15-7.00,P=0.024）, and total radiotherapy dose ≥60 Gy （OR=4.76, 95%CI: 1.68-13.50,P=0.003） were independent risk factors for symptomatic RP. RP occurred earlier in patients who received immunotherapy before thoracic radiotherapy [68.5 d （47.0 d, 101.8 d）] than in patients who received immunotherapy after thoracic radiotherapy [117.5 d （79.0 d, 166.3 d）], with a statistically significant difference （Z=2.54,P=0.010）.ConclusionThe incidence of symptomatic RP is high in patients who receive both thoracic radiotherapy and immunotherapy. The history of COPD, thoracic radiotherapy concurrent with immunotherapy, and the total radiotherapy dose ≥60 Gy are independent influencing factors of symptomatic RP in patients with thoracic radiotherapy combined with immunotherapy. Symptomatic RP occurs earlier in patients who receive immunotherapy before thoracic radiotherapy than in patients who receive immunotherapy after thoracic radiotherapy.

Key words:Lung neoplasms,Chemoradiotherapy,Radiation pneumonitis,Immune checkpoint inhibitor-related pneumonia

Huang Huayu, Song Qibin, Gong Hongyun, Song Jia. Analysis on the incidence and risk factors of pneumonia in patients with lung cancer receiving thoracic radiotherapy and immunotherapy[J]. Journal of International Oncology, 2022, 49(12): 718-723.

Figures/Tables2

一般临床特征	症状性RP （n=42）	无症状性RP （n=95）	χ²值	P值	一般临床特征	症状性RP （n=42）	无症状性RP （n=95）	χ²值	P值
性别					PD-L1表达
男	36	72	1.72	0.190	<1%	7	14	1.90	0.593
女	6	23	1.72	0.190	1%~49%	10	18
年龄（岁）					≥50%	9	15
<70	36	81	0.01	0.945	未知	16	48
≥70	6	14	0.01	0.945	免疫治疗周期（个）
吸烟史					<6	21	50	0.08	0.776
无	8	45	9.85	0.002	≥6	21	45	0.08	0.776
有	34	50	9.85	0.002	化疗周期（个）
PS 评分（分）					<6	14	34	0.08	0.781
0	6	23	1.72	0.190	≥6	28	61	0.08	0.781
1	36	72	1.72	0.190	胸部放疗同步免疫治疗
COPD史					是	28	42	5.88	0.015
无	16	81	31.34	<0.001	否	14	53	5.88	0.015
有	26	14	31.34	<0.001	胸部放疗同步化疗
肺部手术史					是	24	44	1.37	0.243
无	36	81	0.01	0.945	否	18	51	1.37	0.243
有	6	14	0.01	0.945	胸部二次放疗
肺癌种类					是	4	6	0.10	0.757
肺原发癌	36	74	1.13	0.289	否	38	89	0.10	0.757
肺转移癌	6	21	1.13	0.289	放疗总剂量（Gy）
TNM分期					<60	8	43	8.57	0.003
Ⅱ~Ⅲ	12	35	0.88	0.347	≥60	34	52	8.57	0.003
Ⅳ	30	60	0.88	0.347	分割方式
免疫抑制剂种类					常规分割	35	67	2.51	0.113
PD-1	37	85	0.06	0.812	大分割	7	28	2.51	0.113
PD-L1	5	10	0.06	0.812	放疗和免疫治疗顺序
					胸部放疗早于免疫治疗	14	40	0.94	0.333
					胸部放疗晚于免疫治疗	28	55	0.94	0.333

变量	B值	Wald值	OR值	95%CI	P值
吸烟史（有/无）	0.09	0.03	1.09	0.37~3.23	0.872
COPD史（有/无）	2.30	17.60	9.96	3.40~29.14	<0.001
胸部放疗同步免疫治疗（是/否）	1.04	5.11	2.84	1.15~7.00	0.024
放疗总剂量（≥60 Gy/<60 Gy）	1.56	8.61	4.76	1.68~13.50	0.003

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