多原发性早期肺癌立体定向放射治疗后疗效及患者预后分析

doi:10.19401/j.cnki.1007-3639.2023.09.005

摘要/Abstract

摘要：

背景与目的：越来越多的多原发性早期肺癌患者选择接受立体定向放射治疗（stereotactic body radiation therapy，SBRT），本研究旨在回顾性分析SBRT的疗效及预后因素。方法：符合纳入标准的2014年8月—2020年12月于上海交通大学医学院附属胸科医院接受SBRT的241例患者进入本研究，对其中的多原发性早期肺癌患者进行疗效及预后因素分析，并采用倾向性评分匹配（propensity score matching，PSM）后，观察与单原发性早期肺癌SBRT效果的差异性。结果：241例接受SBRT的早期肺癌患者纳入本研究，其中多原发性早期肺癌94例，3和5年局部控制率（local control rate，LC）、无进展生存率（progression-free survival，PFS）和总生存率（overall survival，OS）分别为87.1%和71.3%、84.0%和66.9%、93.3%和79.3%。多原发性早期肺癌患者无3级以上肺炎毒性率，合计毒性率为54.3%，24例（25.5%）患者出现2级毒性。18例（19.1%）出现复发，其中多原发性早期肺癌患者出现局部复发、区域复发、远处转移及不确定性死亡分别为3例（3.2%）、1例（1.1%）、12例（12.7%）及2例（2.1%）。PSM前，多原发性早期肺癌患者与单原发性早期肺癌患者的临床特征存在显著差异。PSM后，多原发性早期肺癌患者和单原发性早期肺癌患者各有56例，在LC（P = 0.291）、PFS（P = 0.954）和OS（P = 0.880）方面差异无统计学意义。94例多原发性早期肺癌患者的SBRT预后因素分析显示，年龄≥70岁是多原发性早期肺癌OS的独立危险因素。同时性和异时性多原发性早期肺癌两组间差异无统计学意义（P = 0.440）。对于59例首-末次治疗间隔5年内的同时性多原发性早期肺癌患者，肿瘤病灶治疗总个数差异无统计学意义（P = 0.232），多次治疗中不同治疗方法差异无统计学意义（P = 0.225）。结论：多原发性早期肺癌SBRT效果较好，与单原发性早期肺癌的疗效相当，SBRT可能是多原发性早期肺癌一种良好的治疗选择。今后需要探讨多原发性早期肺癌基于年龄和肿瘤生物学行为的病灶局部干预策略和技术。

关键词: 多原发性早期肺癌, 立体定向放射治疗, 倾向性评分匹配, 预后

Abstract:

Background and purpose: More and more patients with multiple primary early-stage lung cancer are choosing to receive stereotactic body radiation therapy (SBRT), and this study aimed to retrospectively analyze the efficacy and prognostic factors of SBRT. Methods: In this study, patients who underwent SBRT at Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine from August 2014 to December 2020 and who met the inclusion criteria were included. Patients with multiple primary early-stage lung cancer were examined for efficacy and prognostic factors. After using propensity score matching (PSM), the difference in efficacy of SBRT between single and multiple primary early-stage lung cancer was observed. Results: This study included 241 early-stage lung cancer patients with SBRT, including 94 patients with multiple primary early-stage lung cancer. The 3- and 5-year local control rate (LC), progression-free survival (PFS) and overall survival (OS) were 87.1% and 71.3%, 84.0% and 66.9%, 93.3% and 79.3% in multiple primary early-stage lung cancer, respectively. Patients with multiple primary early-stage lung cancer did not experience any grade 3 or higher pulmonary toxicity with an overall toxicity incidence of 54.3%, and grade 2 toxicity occurred in 24 patients (25.5%). There was a total of 18 (19.1%) recurrences, and there were 3 (3.2%), 1 (1.1%), 12 (12.7%) and 2 (2.1%) patients with multiple primary early-stage lung cancers who experienced local recurrence, regional recurrence, distant metastasis and uncertain death, respectively. Patients with multiple primary early-stage lung cancer and those with single primary early-stage lung cancer had significant differences in clinical features prior to PSM. After PSM, there were 56 patients with multiple primary early-stage lung cancer and 56 patients with single primary early-stage lung cancer, and there was no statistically significant difference in LC (P = 0.291), PFS (P = 0.954) and OS (P = 0.880). Age≥70 years was an independent risk factor for OS of multiple primary early-stage lung cancer, according to an analysis of the prognostic variables of SBRT in 94 patients with multiple primary early-stage lung cancer. Regarding synchronous (≤180 d) and metachronous (>180 d) multiple primary early-stage lung cancer, there was no discernible difference between the two groups (P = 0.440). There was no significant difference in the total number of treatments for multiple primary early-stage lung cancer (P = 0.232) and no significant difference in the type of treatment for multiple primary early-stage lung cancer (P = 0.225) among 59 patients with synchronous multiple primary early-stage lung cancer within 5 years of the first-to-last treatment interval. Conclusion: SBRT has a strong and comparable efficacy for multiple primary early-stage lung cancer compared with single primary early-stage lung cancer, making it a viable treatment choice. Based on age and tumor biological behavior of the lesion, future strategies and procedures for local intervention of multiple primary early-stage lung cancer need to be investigated.

Key words: Multiple primary early-stage lung cancer, Stereotactic body radiation therapy, Propensity score matching, Prognosis

中图分类号:

R734.2

吴晗, 杨章孺, 冯雯, 曾琬琴, 郭金栋, 李洪选, 王常禄, 王家明, 吕长兴, 张琴, 余雯, 蔡旭伟, 傅小龙. 多原发性早期肺癌立体定向放射治疗后疗效及患者预后分析[J]. 中国癌症杂志, 2023, 33(9): 844-856.

WU Han, YANG Zhangru, FENG Wen, ZENG Wanqin, GUO Jindong, LI Hongxuan, WANG Changlu, WANG Jiaming, LÜ Changxing, ZHANG Qin, YU Wen, CAI Xuwei, FU Xiaolong. The efficacy and prognosis analysis after stereotactic body radiotherapy for multiple primary early-stage lung cancer[J]. China Oncology, 2023, 33(9): 844-856.

图/表 11

图1

表1

PSM前后患者的临床特征分析"

Clinical characteristic	Before PSM			After PSM
Clinical characteristic	Single primary early-stage lung cancer (n=147)	Multiple primary early-stage lung cancer (n=94)	P value	Single primary early-stage lung cancer (n=56)	Multiple primary early-stage lung cancer (n=56)	Pvalue
Median follow-up (range)/month	33 (1-83)	44 (1-95)		32.5 (2-81)	37 (1-93)
Gender			0.001			0.686
Male	109 (74.1)	50 (53.2)		37 (66.1)	39 (69.6)
Female	38 (25.9)	44 (46.8)		19 (33.9)	17 (30.4)
Age/year			<0.001			0.344
<74	53 (36.1)	64 (68.1)		27 (48.2)	32 (57.1)
≥74	94 (63.9)	30 (31.9)		29 (51.8)	24 (42.9)
Tumor Location			0.048			0.303
Upper left	43 (29.3)	20 (21.3)		17 (30.4)	17 (30.4)
Lower left	12 (8.2)	17 (18.1)		3 (5.4)	8 (14.3)
Upper right	51 (34.7)	23 (24.5)		21 (37.5)	13 (23.2)
Middle right	11 (7.5)	11 (11.7)		5 (8.9)	8 (14.3)
Lower right	30 (20.4)	23 (24.5)		10 (17.9)	10 (17.9)
Radiotherapy dose/Gy			0.016			0.451
48	0 (0.0)	1 (1.1)		0 (0.0)	0 (0.0)
50	85 (57.8)	68 (72.3)		41 (73.2)	37 (66.1)
55	0 (0.0)	2 (2.1)		0 (0.0)	1 (1.8)
60	41 (27.9)	11 (11.7)		11 (19.6)	9 (16.1)
64	3 (2.0)	1 (1.1)		1 (1.8)	1 (1.8)
70	18 (12.2)	11 (11.7)		3 (5.4)	8 (14.3)
Radiotherapy dose fraction			0.028			0.381
4	32 (21.8)	23 (24.5)		10 (17.9)	12 (21.4)
5	53 (36.1)	43 (45.7)		30 (53.6)	24 (42.9)
8	39 (26.5)	10 (10.6)		10 (17.9)	8 (14.3)
10	23 (15.6)	18 (19.1)		6 (10.7)	12 (21.4)
BED/Gy			0.042			0.256
<105	57 (38.8)	49 (52.1)		33 (58.9)	27 (48.2)
≥105	90 (61.2)	45 (47.9)		23 (41.1)	29 (51.8)
Pathology			0.001			0.693
No	78 (53.1)	70 (74.5)		37 (66.1)	35 (62.5)
Yes	69 (46.9)	24 (25.5)		19 (33.9)	21 (37.5)
T stage			0.001			0.457
cT_is	7 (4.8)	13 (13.8)		3 (5.4)	4 (7.1)
cT_1mi	1 (0.7)	4 (4.3)		0 (0.0)	0 (0.0)
T_1a	9 (6.1)	12 (12.8)		7 (12.5)	4 (7.1)
T_1b	53 (36.1)	38 (40.4)		24 (42.9)	25 (44.6)
T_1c	41 (27.9)	20 (21.3)		15 (26.8)	17 (30.4)
T_2a	28 (19.0)	3 (3.2)		7 (12.5)	3 (5.4)
T_2b	5 (3.4)	3 (3.2)		0 (0.0)	2 (3.6)
T₃	3 (2.0)	1 (1.1)		0 (0.0)	1 (1.8)
Tumor density			<0.001			1.000
Subsolid	48 (32.7)	56 (59.6)		27 (48.2)	27 (48.2)
Solid	99 (67.3)	38 (40.4)		29 (51.8)	29 (51.8)
PET/CT			0.012			0.841
No	51 (34.7)	48 (51.1)		18 (32.1)	19 (33.9)
Yes	96 (65.3)	46 (48.9)		38 (67.9)	37 (66.1)
Underlying disease			0.394			0.850
No	56 (38.1)	41 (43.6)		26 (46.4)	27 (48.2)
Yes	91 (61.9)	53 (56.4)		30 (53.6)	29 (51.8)
Smoking status			0.071			0.847
No	88 (59.9)	67 (71.3)		34 (60.7)	33 (58.9)
Yes	59 (40.1)	27 (28.7)		22 (39.3)	23 (41.1)
Family history of tumors			0.010			0.219
No	130 (88.4)	75 (79.8)		49 (87.5)	44 (78.6)
Family history of lung cancer	8 (5.4)	16 (17.0)		4 (7.1)	10 (17.9)
Family history of other tumors	9 (6.1)	3 (3.2)		3 (5.4)	2 (3.6)
Occupational exposure			0.146			0.568
No	134 (91.2)	80 (85.1)		50 (89.3)	48 (85.7)
Yes	13 (8.8)	14 (14.9)		6 (10.7)	8 (14.3)
ECOG performance status			0.212			0.590
0	45 (30.6)	24 (25.5)		20 (35.7)	15 (26.8)
1	91 (61.9)	67 (71.3)		34 (60.7)	39 (69.6)
2	11 (7.5)	3 (3.2)		2 (3.6)	2 (3.6)
Indications for surgery			0.001			0.333
No	46 (31.3)	11 (11.7)		9 (16.1)	11 (19.6)
Yes	3 (2.0)	0 (0.0)		2 (3.6)	0 (0.0)
Uncertain	98 (66.7)	83 (88.3)		45 (80.4)	45 (80.4)

表1

表2

图2

图3

表3

94例多原发性早期肺癌患者生存预后的单因素和多因素分析"

Clinical characteristic	Multiple primary early-stage lung cancer n (%)	Univariate analysis			Multivariable analysis
Clinical characteristic	Multiple primary early-stage lung cancer n (%)	HR	95% CI	P value (OS)	HR	95% CI	P value (OS)
Median follow-up (range)/month	63.5 (19-170)
Gender		0.186	0.041-0.842	0.015	0.356	0.063-2.003	0.241
Male	50 (53.2)
Female	44 (46.8)
Age/year		6.142	1.359-27.761	0.007	6.180	1.263-30.249	0.025
<70	46 (48.9)
≥70	48 (51.1)
Tumor location		2.686	0.589-12.257	0.185
Ipsilateral	27 (28.7)
Bilateral	67 (71.3)
Average BED/Gy		0.918	0.304-2.777	0.880
<105	46 (48.9)
≥105	48 (51.1)
Highest T stage		1.532	0.906-2.592	0.003	1.515	0.876-2.618	0.137
cT_1mi	1 (1.1)
T_1a	8 (8.5)
T_1b	36 (38.3)
T_1c	25 (26.6)
T_2a	19 (20.2)
T_2b	3 (3.2)
T₃	2 (2.1)
Underlying disease		0.884	0.295-2.655	0.827
No	41 (43.6)
Yes	53 (56.4)
Smoking status		3.504	1.068-11.499	0.027	2.263	0.590-8.679	0.234
No	67 (71.3)
Yes	27 (28.7)
Family history of tumors		0.412	0.066-2.550	0.581
No	75 (79.8)
Family history of lung cancer	16 (17.0)
Family history of other tumors	3 (3.2)
Occupational exposure		0.039	0.000-35.941	0.145
No	80 (85.1)
Yes	14 (14.9)
ECOG performance status		1.551	0.509-4.722	0.743
0	24 (25.5)
1	67 (71.3)
2	3 (3.2)
Clinical diagnosis before the first treatment		0.619	0.181-2.110	0.440
Synchronous (≤180 d)	65 (69.1)
Metachronous (>180 d)	29 (30.9)
Total number of treatments in multiple primary early-stage lung cancer		0.237	0.065-0.862	0.019	0.393	0.104-1.492	0.170
1	24 (25.5)
≥2	70 (74.5)
Type of treatment				-			-
Single SBRT in Single primary early-stage lung cancer	24 (25.5)
Treatment in multiple primary early-stage lung cancer
SBRT only	15 (16.0)
Surgery+SBRT	55 (58.5)
First-last treatment interval				-			-
No other local treatment after SBRT	24 (25.5)
≤1 year	17 (18.1)
>1 year, ≤3 years	16 (17.0)
>3 years, ≤5 years	17 (18.1)
>5 years	20 (21.3)

表3

图4

图5

表4

图6

图7

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Number of lesions	Follow-up/year	Before PSM			After PSM
Number of lesions	Follow-up/year	LC	PFS	OS	LC	PFS	OS
Single primary early-stage lung cancer	1	91.4	88.8	95.1	96.3	92.7	94.5
	3	80.3	71.6	83.0	87.8	77.4	83.8
	5	70.9	51.8	59.6	87.8	63.5	65.2
Multiple primary early-stage lung cancer	1	93.5	91.4	96.8	90.8	87.3	94.6
	3	87.1	84.0	93.3	83.6	78.5	88.7
	5	71.3	66.9	79.3	70.1	62.5	72.7