Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma: analysis of 653 cases

doi:10.12122/j.issn.1673-4254.2024.05.22

Abstract

Abstract:

Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). Results In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P<0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P<0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P<0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P<0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P<0.05; HR=1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P<0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P<0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Key words: stage IB, lung adenocarcinoma, adjuvant chemotherapy, epidermal growth factor receptor mutation, targeted therapy, disease-free survival

Leilei SHEN, Ying CHEN, Tianyang YUN, Juntang GUO, Xi LIU, Tao ZHANG, Chaoyang LIANG, Yang LIU. Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma: analysis of 653 cases[J]. Journal of Southern Medical University, 2024, 44(5): 989-997.

Figures/Tables 10

References 35

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Characteristic No.	TKIs group (n=111)	CT group (n=108)	CO group (n=434)	P
Gender				0.003
Male	38 (34.2)* ^#	57 (52.8)	226 (52.1)
Female	73 (65.8)* ^#	51 (47.2)	208 (47.9)
Age (year)	60.66±9.05*	57.45±9.07 ^#	61.08±8.95	0.001
≤65	72 (64.9)*	88 (81.5) ^#	287 (66.1)	0.006
>65	39 (35.1)*	20 (18.5) ^#	147 (33.9)	0.006
Smoking history	26 (23.4)	40 (37.0)	135 (31.1)	0.091
Family history of lung cancer	16 (14.4)	12 (11.1)	47 (10.8)	0.584
CEA abnormality	18 (16.2) ^#	9 (8.3)	33 (7.6)	0.019
Diabetes mellitus	7 (6.3)	7 (6.5)	51 (11.8)	0.096
Hypertension	31 (27.9)	22 (20.4)	121 (27.9)	0.280
Cardiovascular disease	8 (7.2)	5 (4.6)	26 (6.0)	0.687
Cerebrovascular disease	4 (3.6)	2 (1.9)	14 (3.2)	0.797
PET-CT	8.00 (3.60, 10.00)	6.85 (3.13, 9.00)	4.85 (2.20, 8.60)	0.175
Tumor location				0.154
RUL	34 (30.6)	34 (31.5)	139 (32.0)
RML	14 (12.6)	5 (4.6)	31 (7.1)
RLL	11(9.9)	22 (20.4)	79 (18.2)
LUL	30 (27.0)	32 (29.6)	104 (24.0)
LLL	22 (19.8)	15 (13.9)	81 (18.78)
CTR	1 (1, 1)	1 (1, 1)	1 (0.87, 1)	0.105
Solid nodule	71 (64.0)	81 (75.0) ^#	271 (62.4)	0.049
Surgical procedure				0.412
Sublobectomy	15 (13.5)	9 (8.3)	43 (9.9)
Lobectomy	96 (86.5)	99 (91.7)	391 (90.1)
LND
Stations	5 (5, 6)	5.5 (3.25, 6)	5 (4, 6)	0.859
Numbers	9 (6, 16)	9.5 (4.5, 16)	10 (7, 16)	0.507
pNx	30 (27.0)	30 (27.8)	114 (26.3)	0.956

Characteristic No.	TKIs group (n=111)	CT group (n=108)	CO group (n=434)	P
Gender				0.003
Male	38 (34.2)* ^#	57 (52.8)	226 (52.1)
Female	73 (65.8)* ^#	51 (47.2)	208 (47.9)
Age (year)	60.66±9.05*	57.45±9.07 ^#	61.08±8.95	0.001
≤65	72 (64.9)*	88 (81.5) ^#	287 (66.1)	0.006
>65	39 (35.1)*	20 (18.5) ^#	147 (33.9)	0.006
Smoking history	26 (23.4)	40 (37.0)	135 (31.1)	0.091
Family history of lung cancer	16 (14.4)	12 (11.1)	47 (10.8)	0.584
CEA abnormality	18 (16.2) ^#	9 (8.3)	33 (7.6)	0.019
Diabetes mellitus	7 (6.3)	7 (6.5)	51 (11.8)	0.096
Hypertension	31 (27.9)	22 (20.4)	121 (27.9)	0.280
Cardiovascular disease	8 (7.2)	5 (4.6)	26 (6.0)	0.687
Cerebrovascular disease	4 (3.6)	2 (1.9)	14 (3.2)	0.797
PET-CT	8.00 (3.60, 10.00)	6.85 (3.13, 9.00)	4.85 (2.20, 8.60)	0.175
Tumor location				0.154
RUL	34 (30.6)	34 (31.5)	139 (32.0)
RML	14 (12.6)	5 (4.6)	31 (7.1)
RLL	11(9.9)	22 (20.4)	79 (18.2)
LUL	30 (27.0)	32 (29.6)	104 (24.0)
LLL	22 (19.8)	15 (13.9)	81 (18.78)
CTR	1 (1, 1)	1 (1, 1)	1 (0.87, 1)	0.105
Solid nodule	71 (64.0)	81 (75.0) ^#	271 (62.4)	0.049
Surgical procedure				0.412
Sublobectomy	15 (13.5)	9 (8.3)	43 (9.9)
Lobectomy	96 (86.5)	99 (91.7)	391 (90.1)
LND
Stations	5 (5, 6)	5.5 (3.25, 6)	5 (4, 6)	0.859
Numbers	9 (6, 16)	9.5 (4.5, 16)	10 (7, 16)	0.507
pNx	30 (27.0)	30 (27.8)	114 (26.3)	0.956

Characteristic	TKIs group (n=111)	CT group (n=108)	CO group (n=434)	P
Tumor diameter(mm)	30.89±5.87	32.10±6.23 ^#	29.74±5.80	0.001
>3 cm	68 (61.3)	75 (69.4)	260 (59.9)	0.192
≤3 cm	43 (38.7)	33 (30.6)	174 (40.1)	0.192
≥1 high-risk factors	105 (94.6)	102 (94.4)	397 (91.5)	0.389
Mucous component	8 (7.2)	11 (10.3)	35 (8.1)	0.706
Micropapillary or solid component	50(45.0)*	67 (62.0) ^#	154 (35.5)	<0.001
VPI	82 (73.9)	88 (81.5)	333 (76.7)	0.397
LVI	7 (6.3) ^#	9 (8.3) ^#	7 (1.6)	<0.001
STAS	12 (10.8) ^#	11 (10.2) ^#	19 (4.4)	0.011
Ki-67 index(≥20%)	36 (42.9)	40 (44.9)	120 (36.8)	0.289
EGFR mutation	111 (100)* ^#	18/44 (40.9) ^#	78/110 (70.9)	<0.001
19 del	52/111 (46.8)	5/18 (27.8)	31/78 (39.7)	-
21 L858R	58/111 (52.2)	8/18 (44.4)	41/78 (52.5)	-
20 T790M/20 ins	0/0	0/3	1/2	-
G719X/S861I/L861Q	1/0/0	1/0/1	1/1/1	-
ALK mutation	0* ^#	4/40 (10)	9/101 (8.9)	0.011
KRAS mutation	1/48 (2.0)	4/37 (10.8)	7/88 (7.9)	0.252
TP53 mutation	9/26 (34.6)	8/20 (40)	15/46 (32.6)	0.893
PD-L1	0 (0, 5)	1.5 (0, 5)	0 (0, 3)	0.240
IASLC grade				0.002
1	9 (8.1) ^#	4 (3.7) ^#	23 (5.3)
2	66 (59.5) ^#	50 (46.3) ^#	280 (64.5)
3	36 (32.4) ^#	54 (50.0) ^#	131 (30.2)

Characteristic	TKIs group (n=111)	CT group (n=108)	CO group (n=434)	P
Tumor diameter(mm)	30.89±5.87	32.10±6.23 ^#	29.74±5.80	0.001
>3 cm	68 (61.3)	75 (69.4)	260 (59.9)	0.192
≤3 cm	43 (38.7)	33 (30.6)	174 (40.1)	0.192
≥1 high-risk factors	105 (94.6)	102 (94.4)	397 (91.5)	0.389
Mucous component	8 (7.2)	11 (10.3)	35 (8.1)	0.706
Micropapillary or solid component	50(45.0)*	67 (62.0) ^#	154 (35.5)	<0.001
VPI	82 (73.9)	88 (81.5)	333 (76.7)	0.397
LVI	7 (6.3) ^#	9 (8.3) ^#	7 (1.6)	<0.001
STAS	12 (10.8) ^#	11 (10.2) ^#	19 (4.4)	0.011
Ki-67 index(≥20%)	36 (42.9)	40 (44.9)	120 (36.8)	0.289
EGFR mutation	111 (100)* ^#	18/44 (40.9) ^#	78/110 (70.9)	<0.001
19 del	52/111 (46.8)	5/18 (27.8)	31/78 (39.7)	-
21 L858R	58/111 (52.2)	8/18 (44.4)	41/78 (52.5)	-
20 T790M/20 ins	0/0	0/3	1/2	-
G719X/S861I/L861Q	1/0/0	1/0/1	1/1/1	-
ALK mutation	0* ^#	4/40 (10)	9/101 (8.9)	0.011
KRAS mutation	1/48 (2.0)	4/37 (10.8)	7/88 (7.9)	0.252
TP53 mutation	9/26 (34.6)	8/20 (40)	15/46 (32.6)	0.893
PD-L1	0 (0, 5)	1.5 (0, 5)	0 (0, 3)	0.240
IASLC grade				0.002
1	9 (8.1) ^#	4 (3.7) ^#	23 (5.3)
2	66 (59.5) ^#	50 (46.3) ^#	280 (64.5)
3	36 (32.4) ^#	54 (50.0) ^#	131 (30.2)

Distribution	Icotinib (n=65)	Gefitinib (n=28)	Furmonertinib/ almonertinib (n=1/2)	Osimertinib (n=15)	Chemotherapy (n=108)
Duration
1 year/2 cycles	25 (38.5)	6 (21.4)	1 (33)	3 (20)	6 (5.6)
2 years/3 cycles	36 (55.4)	16 (57.1)	2 (66)	12 (80)	8 (7.4)
3 years/4 cycles	2 (3.1)	5 (17.9)	0	0	94 (87)
5 years	2 (3.1)	1 (3.6)	0	0	-
Economy cost (RMB/year)	3.9×10⁴	1.4×10⁴	Not applicable	6.4×10⁴	Not applicable
Adverse events
Rash	24 (36.9)	11 (40)	2 (66)	3 (20)	0
Paronychia	11 (16.9)	7 (25)	1 (33)	4 (26.7)	0
Interstitial pneumonia	0	0	0	0	0
Thrombocytopenia	1 (1.5)	1 (3.6)	0	1 (1.5)	21 (19.4)
Leukopenia	1 (1.5)	1 (3.6)	0	1 (1.5)	64 (59.3)
Diarrhea	13 (20)	6 (30)	1 (33)	6 (40)	5 (4.6)
Nausea	2 (3)	2 (7.1)	0	3 (20)	60 (55.6)
Decreased appetite	1 (1.5)	1 (3.6)	1 (33)	2 (13.3)	20 (18.5)
Grade ≥3	5 (7.7)	4 (14.3)	0	1 (6.5)	48 (44.4)