接受胸部放疗和免疫治疗肺癌患者肺炎发生率及影响因素分析

摘要/Abstract

摘要：

目的分析接受胸部放疗和免疫治疗的肺原发癌和肺转移癌患者放射性肺炎（RP）和免疫治疗相关性肺炎（CIP）的发生率、危险因素及发生时间。方法回顾性分析2019年1月至2022年1月在武汉大学人民医院行胸部放疗且至少接受一周期免疫检查点抑制剂治疗的137例肺原发癌和肺转移癌患者的临床病理资料。根据患者临床症状、胸部薄层CT确定患者有无RP、CIP发生。对患者临床资料和治疗计划等指标进行单因素及多因素分析评价症状性RP发生相关危险因素。比较症状性RP发生时间与胸部放疗和免疫治疗顺序的关系。结果137例接受胸部放疗和免疫治疗的肺原发癌和肺转移癌患者中有42例（30.7%）患者发生症状性RP，包括2级RP 33例（24.1%）、3级RP 6例（4.4%）、4级RP 1例（0.7%）、5级RP 2例（1.5%）。胸部放疗同步免疫治疗与非同步患者的症状性RP发生率分别为40.0%（28/70）和20.9%（14/67），严重RP发生率分别为10.0（7/70）和3.0%（2/67）。137例患者中有11例（8.0%）患者发生CIP，包括2级CIP 4例（2.9%）、3级CIP 6例（4.4%）、5级CIP 1例（0.7%）。有54.5%（6/11）的CIP患者先前或者同时合并症状性RP。单因素分析结果显示，吸烟史（χ²=9.85，P=0.002）、慢性阻塞性肺病（COPD）史（χ²=31.34，P<0.001）、胸部放疗同步免疫治疗（χ²=5.88，P=0.015）、放疗总剂量（χ²=8.57，P=0.003）均与症状性RP发生有关。多因素logistic回归分析显示，COPD史（OR=9.96，95%CI为3.40~29.14，P<0.001）、胸部放疗同步免疫治疗（OR=2.84，95%CI为1.15~7.00，P=0.024）、放疗总剂量≥60 Gy（OR=4.76，95%CI为1.68~13.50，P=0.003）均为症状性RP发生的独立危险因素。胸部放疗前接受免疫治疗的患者发生症状性RP的时间[68.5 d（47.0 d，101.8 d）]早于胸部放疗后接受免疫治疗患者时间[117.5 d（79.0 d，166.3 d）]，差异具有统计学意义（Z=2.54，P=0.010）。结论胸部放疗联合免疫治疗患者的症状性RP发生率较高。COPD史、胸部放疗同步免疫治疗、放疗总剂量≥60 Gy是胸部放疗联合免疫治疗患者发生症状性RP的独立影响因素。胸部放疗前接受免疫治疗的患者发生症状性RP的时间早于胸部放疗后接受免疫治疗患者。

关键词:肺肿瘤,化放疗,辐射性肺炎,免疫治疗相关性肺炎

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

黄华玉, 宋启斌, 龚虹云, 宋佳. 接受胸部放疗和免疫治疗肺癌患者肺炎发生率及影响因素分析[J]. 国际肿瘤学杂志, 2022, 49(12): 718-723.

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.

图/表2

表1

137例接受过胸部放疗和免疫治疗的肺癌患者发生症状性RP的单因素分析（例）"

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

表1

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

表2

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