3.1 Characteristics of Study Participants
Between October 2013 and December 2018, 190 patients participated in this study, among which 23 were excluded as 3 were confirmed with other tumors, 3 received surgeries, 1 had no definite stage, 5 had no complete clinical data, 4 were in the middle of treatment and 4 exited, leaving the final number of patients eligible for analysis to be 168 (Figure. 1). The lost 12 patients had finished 4–6 cycles of chemotherapy and were follow-up by at least 1 time, making them be evaluated as censored data. Among the final participants, 86 (46.2%) were placed in the TCM group and 86 (53.8%) were in the non-TCM group. No statistically significant difference existed between the two groups in terms of age, sex, disease stage at initial diagnosis, ECOG performance score at baseline, pleural effusions at initial diagnosis, brain metastases at initial diagnosis, chemotherapy regimens, history of TRT, history of PCI, smoking history, family history (Table 1).
Table 1
Patient demographics and baseline characteristics.
|
TCM Group (n = 85)
|
Non-TCM Group (n = 83)
|
All patients (n = 168)
|
P value
|
Median age at baseline, y (range)
|
61 (23, 75)
|
60 (40, 75)
|
60 (23, 75)
|
0.815
|
Sex
|
|
|
|
|
Male
|
64 (75.3)
|
63 (75.9)
|
127 (75.6)
|
0.927
|
Female
|
21 (24.7)
|
20 (24.1)
|
41 (24.4)
|
|
Disease stage at initial diagnosis
|
|
|
|
|
Limited-stage
|
45 (52.9)
|
52 (62.7)
|
97 (57.7)
|
0.203
|
Extensive-stage
|
40 (47.1)
|
31 (37.3)
|
71 (42.3)
|
|
ECOG performance score at baseline
|
|
|
|
|
0
|
1 (1.2)
|
1 (1.2)
|
2 (1.2)
|
1.000
|
1
|
77 (90.6)
|
75 (90.4)
|
152 (90.5)
|
|
2
|
7 (8.2)
|
7 (8.4)
|
14 (8.3)
|
|
Pleural effusions at initial diagnosis
|
|
|
|
|
Yes
|
14 (16.5)
|
16 (19.3)
|
30 (17.9)
|
0.635
|
No
|
71 (83.5)
|
67 (80.7)
|
138 (82.1)
|
|
Brain metastases at initial diagnosis
|
|
|
|
|
Yes
|
8 (9.4)
|
2 (2.4)
|
10 (6.0)
|
0.111
|
No
|
77 (90.6)
|
81 (97.6)
|
158 (94.0)
|
|
Chemotherapy regimens
|
|
|
|
|
EP
|
46 (54.1)
|
53 (63.9)
|
99 (58.9)
|
0.144
|
EC
|
36 (42.4)
|
24 (28.9)
|
60 (35.7)
|
|
Othera
|
3 (3.5)
|
6 (7.2)
|
9 (5.4)
|
|
History of TRT
|
|
|
|
|
Yes
|
60 (70.6)
|
60 (72.3)
|
120 (71.4)
|
0.807
|
No
|
25 (29.4)
|
23 (27.7)
|
48 (28.6)
|
|
History of PCI
|
|
|
|
|
Yes
|
26 (30.6)
|
29 (34.9)
|
55 (32.7)
|
0.548
|
No
|
59 (69.4)
|
54 (65.1)
|
113 (67.3)
|
|
Smoking history
|
|
|
|
|
Yes
|
46 (54.1)
|
51 (61.4)
|
97 (57.7)
|
0.336
|
No
|
39 (45.9)
|
32 (38.6)
|
71 (42.3)
|
|
Family history
|
|
|
|
|
Yes
|
15 (17.6)
|
16 (19.3)
|
31 (18.5)
|
0.785
|
no
|
70 (82.4)
|
67 (80.7)
|
137 (81.5)
|
|
NOTE: Data shown are N (%) unless otherwise indicated. |
Abbreviations: ECOG, Eastern Cooperative Oncology Group; EP, Etoposide and cisplatin; EC, Etoposide and carboplatin; TRT, thoracic radiation therapy; PCI, Prophylactic Cranial Irradiation. aOther chemotherapy regimens included Etoposide and lobaplatin/nedaplatin |
3.2 OS and PFS
OS and PFS were calculated to evaluate the impact of TCM therapy on prognosis. The median OS was 23.4 months in patients who received TCM therapy, whereas OS in patients without TCM therapy was 20.1 months (P = 0.301, Fig. 2). The median PFS registered 11.83 months and 8.60 months in the TCM and the non-TCM group respectively. There was a significant difference between the groups in PFS (P = 0.004, Fig. 3). The use of Cox proportional hazards regression for confounder control yielded that TCM was a significant clinical factor for PFS (adjusted HR 0.552, 95% CI 0.389–0.783, P = 0.01, Fig. 4), but was not a significant clinical factor for OS compared with non-TCM (P > 0.05).
Subgroup analysis stratified by different stages was performed. For LS-SCLC, the median OS was 34.5 months in the TCM group, and that in the non-TCM group was 22.6 months (P = 0.586, Fig. 5). The median PFS registered 14.73 months and 9.2 months in the two groups respectively (P = 0.040, Fig. 6). For ES-SCLC, the median OS for the TCM group was 18.5 months compared with 17.37 months for the non-TCM group (P = 0.162, Fig. 7). The median PFS for patients in the TCM group was 9.53 months, whereas, for patients in the non-TCM group, the median PFS was 7.47 months (P = 0.007, Fig. 8).
3.3 ORR and DCR
ORR and DCR were evaluated (Table 2). After two cycles of treatments, ORR of the TCM group recorded 85.88% compared with 75.90% of the non-TCM group. DCR of the TCM group was 100% whereas, for the non-TCM group, the percentage was 98.80%. When four cycles of treatments were finished, ORR of the TCM group was 61.2% better than that of the non-TCM group (43.4%). Meanwhile, DCR for the TCM group notched up 95.3% compared with 89.2% for the non-TCM group.
Table 2
ORR and DCR for SCLC with or without TCM
|
CR
|
PR
|
SD
|
PD
|
ORR
|
DCR
|
After second cycle treatment
|
|
|
|
|
|
|
TCM
|
2(2.4%)
|
71(83.5%)
|
12(14.1%)
|
0(0%)
|
73(85.88%)
|
85(100%)
|
Non-TCM
|
0(0%)
|
63(75.9%)
|
19(22.9%)
|
1(1.2%)
|
63(75.90%)
|
82(98.80%)
|
After fourth cycle treatment
|
|
|
|
|
|
|
TCM
|
0(0%)
|
52(61.2%)
|
29(34.1%)
|
4(4.7%)
|
52(61.2%)
|
81(95.3%)
|
Non-TCM
|
2(2.4%)
|
34(41%)
|
38(45.8%)
|
9(10.8%)
|
36(43.4%)
|
74(89.2%)
|
3.4 Adverse Events
The number of cases with leukopenia, anorexia, constipation, fatigue, nausea in patients receiving TCM treatment is lower than that in patients without TCM (P < 0.05, Table 3). There was no difference between the two groups for other adverse events (P > 0.05, Table 3).
Table 3
The number of cases with the highest adverse reactions during treatment
|
Grade 1/2
|
Grade 3/4
|
P
|
|
TCM
|
Non-TCM
|
TCM
|
Non-TCM
|
Hematologic
|
|
|
|
|
|
Anemia
|
40(47.1%)
|
50(60.2%)
|
2(2.4%)
|
6(7.2)
|
0.032
|
Leukopenia
|
59(69.4%)
|
48(57.8%)
|
6(7.1%)
|
20(24.1)
|
0.009*
|
Neutropenia
|
44(51.8%)
|
31(37.3%)
|
7(8.2%)
|
13(15.7)
|
0.112
|
Thrombocytopenia
|
7(8.2%)
|
8(9.6%)
|
0(0)
|
2(2.4)
|
0.482
|
Nonhematologic
|
|
|
|
|
|
ALT increase
|
3(3.5%)
|
1(2.4%)
|
0(0)
|
0(0)
|
0.630
|
AST increase
|
2(2.4%)
|
4(4.8%)
|
0(0)
|
0(0)
|
0.656
|
ALP increase
|
1(1.2%)
|
1(1.2%)
|
0(0)
|
0(0)
|
1.000
|
Tbil increase
|
4(4.7%)
|
2(2.4%)
|
0(0)
|
0(0)
|
0.699
|
Cr increase
|
0(0)
|
5(6.0%)
|
0(0)
|
0(0)
|
0.065
|
Anorexia
|
49(57.6%)
|
58(69.9%)
|
1(1.2%)
|
8(9.6%)
|
0.002*
|
Constipation
|
22(25.9%)
|
32(38.6%)
|
1(1.2%)
|
8(9.6%)
|
0.004*
|
Fatigue
|
50(58.8%)
|
71(85.5%)
|
2(2.4%)
|
4(4.8%)
|
0.000*
|
Nausea
|
28(32.9%)
|
50(60.1%)
|
4(4.7%)
|
7(8.4%)
|
0.000*
|
Vomiting
|
19(22.4%)
|
25(30.1%)
|
0(0)
|
2(2.4%)
|
0.150
|
*P < 0.05 |