World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 5, October 2024, pages 769-776

Prognostic Implications of Timing of Immunotherapy in Stage IV Non-Small Cell Lung Cancer

Figure 1. Selection criteria according to CONSORT diagram. Deidentified cases were released from the National Cancer Database. IO: immunotherapy.

Figure 2. Immunotherapy within the first 30 days of chemotherapy treatment improves overall survival in patients with stage IV non-small cell lung cancer, compared to delayed or no immunotherapy statuses. Median survival months and log-rank P values are shown. CT: chemotherapy; IO: immunotherapy; OS: overall survival.

Figure 3. Propensity score matching analysis of early (30 days) and delayed (31 - 60 days) immunotherapy groups. Matched cases were compared for OS. CT: chemotherapy; IO: immunotherapy; OS: overall survival.

**Table 1.** Clinical Characteristics of Eligible Cases (N (%))
Factors	Immunotherapy	Total	P value
CD: Charlson-Deyo.
Total	3,291 (100%)	237 (100%)	4,309 (100%)	7,837 (100%)
Institution
Academic	965 (29%)	67 (28%)	1,227 (28%)	2,259 (29%)	0.71
Other	2,326 (71%)	170 (72%)	3,082 (72%)	5,578 (71%)
Age
70 and older	1,075 (33%)	83 (35%)	1,573 (37%)	2731 (35%)	< 0.01
Less than 70	2,216 (67%)	154 (65%)	2,736 (63%)	5,106 (65%)
Sex
Male	1,838 (56%)	123 (52%)	2,536 (59%)	4,497 (57%)	< 0.01
Female	1,453 (44%)	114 (48%)	1,773 (41%)	3,340 (43%)
Race
White	2,789 (85%)	212 (89%)	3,540 (82%)	6,541 (83%)	< 0.01
Other	502 (15%)	25 (11%)	769 (18%)	1,296 (17%)
CD score
0 - 1	3,138 (95%)	226 (95%)	4,131 (96%)	7,495 (96%)	0.54
2 - 3	153 (5%)	11 (5%)	178 (4%)	342 (4%)
Year of diagnosis
2017	1,164 (35%)	116 (49%)	2,809 (65%)	4,089 (52%)	< 0.01
2018	2,127 (65%)	121 (51%)	1,500 (35%)	3,748 (48%)
Histology
Adenocarcinoma	2,785 (85%)	159 (67%)	2,634 (61%)	5,578 (71%)	< 0.01
Other	506 (15%)	78 (33%)	1,675 (39%)	2,259 (29%)
Clinical T stage
cT3-4	1,554 (47%)	129 (54%)	2,214 (51%)	3,897 (50%)	< 0.01
Other	1,737 (53%)	108 (46%)	2,095 (49%)	3,940 (50%)
Clinical N stage
cN2-3	2,250 (68%)	153 (65%)	2,905 (67%)	5,308 (68%)	0.39
Other	1,041 (32%)	84 (35%)	1,404 (33%)	2,529 (32%)
Clinical M stage
cM1BC	2,240 (68%)	162 (68%)	2,790 (65%)	5,192 (66%)	< 0.01
Other	1,051 (32%)	75 (32%)	1,519 (35%)	2,645 (34%)
Surgery
Yes	63 (2%)	4 (2%)	69 (2%)	136 (2%)	0.58
No	3,228 (98%)	233 (98%)	4,240 (98%)	7,701 (98%)
Radiation
Yes	1,237 (38%)	116 (49%)	1,947 (45%)	3,300 (42%)	< 0.01
No	2,054 (62%)	121 (51%)	2,362 (55%)	4,537 (58%)
Brain metastasis
Yes	771 (23%)	52 (22%)	918 (21%)	1,741 (22%)	0.09
No	2,520 (77%)	185 (78%)	3,391 (79%)	6,096 (78%)
Liver metastasis
Yes	651 (20%)	49 (21%)	869 (20%)	1,569 (20%)	0.89
No	2,640 (80%)	188 (79%)	3,440 (80%)	6,268 (80%)

Table 1. Clinical Characteristics of Eligible Cases (N (%))

Factors

Immunotherapy

Total

P value

Yes

Starting in

0 - 30 days

31 - 60 days

CD: Charlson-Deyo.

Total

3,291 (100%)

237 (100%)

4,309 (100%)

7,837 (100%)

Institution

Academic

965 (29%)

67 (28%)

1,227 (28%)

2,259 (29%)

0.71

Other

2,326 (71%)

170 (72%)

3,082 (72%)

5,578 (71%)

Age

70 and older

1,075 (33%)

83 (35%)

1,573 (37%)

2731 (35%)

< 0.01

Less than 70

2,216 (67%)

154 (65%)

2,736 (63%)

5,106 (65%)

Sex

Male

1,838 (56%)

123 (52%)

2,536 (59%)

4,497 (57%)

< 0.01

Female

1,453 (44%)

114 (48%)

1,773 (41%)

3,340 (43%)

Race

White

2,789 (85%)

212 (89%)

3,540 (82%)

6,541 (83%)

< 0.01

Other

502 (15%)

25 (11%)

769 (18%)

1,296 (17%)

CD score

0 - 1

3,138 (95%)

226 (95%)

4,131 (96%)

7,495 (96%)

0.54

2 - 3

153 (5%)

11 (5%)

178 (4%)

342 (4%)

Year of diagnosis

2017

1,164 (35%)

116 (49%)

2,809 (65%)

4,089 (52%)

< 0.01

2018

2,127 (65%)

121 (51%)

1,500 (35%)

3,748 (48%)

Histology

Adenocarcinoma

2,785 (85%)

159 (67%)

2,634 (61%)

5,578 (71%)

< 0.01

Other

506 (15%)

78 (33%)

1,675 (39%)

2,259 (29%)

Clinical T stage

cT3-4

1,554 (47%)

129 (54%)

2,214 (51%)

3,897 (50%)

< 0.01

Other

1,737 (53%)

108 (46%)

2,095 (49%)

3,940 (50%)

Clinical N stage

cN2-3

2,250 (68%)

153 (65%)

2,905 (67%)

5,308 (68%)

0.39

Other

1,041 (32%)

84 (35%)

1,404 (33%)

2,529 (32%)

Clinical M stage

cM1BC

2,240 (68%)

162 (68%)

2,790 (65%)

5,192 (66%)

< 0.01

Other

1,051 (32%)

75 (32%)

1,519 (35%)

2,645 (34%)

Surgery

Yes

63 (2%)

4 (2%)

69 (2%)

136 (2%)

0.58

3,228 (98%)

233 (98%)

4,240 (98%)

7,701 (98%)

Radiation

Yes

1,237 (38%)

116 (49%)

1,947 (45%)

3,300 (42%)

< 0.01

2,054 (62%)

121 (51%)

2,362 (55%)

4,537 (58%)

Brain metastasis

Yes

771 (23%)

52 (22%)

918 (21%)

1,741 (22%)

0.09

2,520 (77%)

185 (78%)

3,391 (79%)

6,096 (78%)

Liver metastasis

Yes

651 (20%)

49 (21%)

869 (20%)

1,569 (20%)

0.89

2,640 (80%)

188 (79%)

3,440 (80%)

6,268 (80%)

**Table 2.** Univariate and Multivariable Cox Regression Analyses for Overall Survival in Patients With Stage IV NSCLC Treated With Combination Therapy (Within 30 Days vs. 30 - 61 Days)
Factors	Univariate	Multivariate
NSCLC: non-small cell lung cancer; HR: hazard ratio; CI: confidence interval; CD: Charlson comorbidity.
Institution
Academic	0.92 (0.84 - 1.01), 0.07	0.94 (0.85 - 1.02), 0.14
Others (reference)
Age
< 70	0.79 (0.72 - 0.86), < 0.01	0.78 (0.71 - 0.85), < 0.01
≥ 70 (reference)
Sex
Female	0.79 (0.72 - 0.85), < 0.01	0.79 (0.73 - 0.86), < 0.01
Male (reference)
Race
Others	0.83 (0.73 - 0.93), < 0.01	0.86 (0.76 - 0.97), 0.01
White (reference)
CD score
0 - 1	1.01 (0.84 - 1.23), 0.92	0.95 (0.79 - 1.15), 0.63
≥ 2 (reference)
Year of diagnosis
2018	0.99 (0.91 - 1.08), 0.82	1.00 (0.92 - 1.09), 0.99
2017 (reference)
Histology
Adenocarcinoma	0.81 (0.73 - 0.90), < 0.01	0.88 (0.79 - 0.99), 0.02
Others (reference)
Clinical T stage
Others	0.92 (0.85 - 1.00), 0.05	0.96 (0.88 - 1.04), 0.34
T3-4 (reference)
Clinical N Stage
Others	0.83 (0.76 - 0.91), < 0.01	0.83 (0.76 - 0.91), < 0.01
N2-3 (reference)
Clinical M stage
Other	0.82 (0.75 - 0.90), <0.01	0.95 (0.86 - 1.04), 0.26
M1BC (reference)
Surgery
Yes	0.70 (0.50 - 0.95), 0.02	0.74 (0.53 - 1.03), 0.07
No (reference)
Radiation
No	0.84 (0.76 - 0.91), < 0.01	0.82 (0.75 - 0.91), < 0.01
Yes (reference)
Brain metastasis
No	0.93 (0.85 - 1.02), 0.13	0.99 (0.88 - 1.10), 0.81
Yes (reference)
Liver metastasis
No	0.63 (0.58 - 0.70), < 0.01	0.64 (0.58 - 0.71), < 0.01
Yes (reference)
Time of immunotherapy
0 - 30 days	0.74 (0.64 - 0.87), < 0.01	0.78 (0.67 - 0.91), < 0.01
31 - 60 days (reference)

Table 2. Univariate and Multivariable Cox Regression Analyses for Overall Survival in Patients With Stage IV NSCLC Treated With Combination Therapy (Within 30 Days vs. 30 - 61 Days)

Factors

Univariate

Multivariate

HR (95% CI), P value

NSCLC: non-small cell lung cancer; HR: hazard ratio; CI: confidence interval; CD: Charlson comorbidity.

Institution

Academic

0.92 (0.84 - 1.01), 0.07

0.94 (0.85 - 1.02), 0.14

Others (reference)

Age

< 70

0.79 (0.72 - 0.86), < 0.01

0.78 (0.71 - 0.85), < 0.01

≥ 70 (reference)

Sex

Female

0.79 (0.72 - 0.85), < 0.01

0.79 (0.73 - 0.86), < 0.01

Male (reference)

Race

Others

0.83 (0.73 - 0.93), < 0.01

0.86 (0.76 - 0.97), 0.01

White (reference)

CD score

0 - 1

1.01 (0.84 - 1.23), 0.92

0.95 (0.79 - 1.15), 0.63

≥ 2 (reference)

Year of diagnosis

2018

0.99 (0.91 - 1.08), 0.82

1.00 (0.92 - 1.09), 0.99

2017 (reference)

Histology

Adenocarcinoma

0.81 (0.73 - 0.90), < 0.01

0.88 (0.79 - 0.99), 0.02

Others (reference)

Clinical T stage

Others

0.92 (0.85 - 1.00), 0.05

0.96 (0.88 - 1.04), 0.34

T3-4 (reference)

Clinical N Stage

Others

0.83 (0.76 - 0.91), < 0.01

N2-3 (reference)

Clinical M stage

Other

0.82 (0.75 - 0.90), <0.01

0.95 (0.86 - 1.04), 0.26

M1BC (reference)

Surgery

Yes

0.70 (0.50 - 0.95), 0.02

0.74 (0.53 - 1.03), 0.07

No (reference)

Radiation

0.84 (0.76 - 0.91), < 0.01

0.82 (0.75 - 0.91), < 0.01

Yes (reference)

Brain metastasis

0.93 (0.85 - 1.02), 0.13

0.99 (0.88 - 1.10), 0.81

Yes (reference)

Liver metastasis

0.63 (0.58 - 0.70), < 0.01

0.64 (0.58 - 0.71), < 0.01

Yes (reference)

Time of immunotherapy

0 - 30 days

0.74 (0.64 - 0.87), < 0.01

0.78 (0.67 - 0.91), < 0.01

31 - 60 days (reference)