Patient Characteristics
From January 2012 to December 2015, 86 patients who underwent SBRT and 79 SLR (include 35 wedge resection and 44 segmentectomy), with a median age at diagnosis of 75 and 65 years, respectively, were met the inclusion criteria and were recruited into the study. Characteristics of patient are shown in Table 1. Compared with those who received SLR, patients treated with SBRT were significantly older and had poorer PS, lower FEV1 and larger tumor diameter. A higher proportion of male patients was treated by SBRT than by SLR (P = 0.019). There was no significant difference in disease stage between SBRT and SLR patients (P = 0.295). There is significant statistical difference in the histologic subtypes for the difference groups (P=0.030). In the group of SBRT, adenocarcinomas, squamous cell carcinomas and other are 46.9%, 30.6% and 22.4%, respectively. In the group of SLR, adenocarcinomas, squamous cell carcinomas and other are 69.4%, 24.5 and 6.1%, respectively.
Table 1. Characteristics of all patients and propensity score matched patients.
|
All patients
|
Propensity score matched patients
|
SBRT (n =86)
|
SLR (n =79)
|
P-value
|
SBRT (n = 49)
|
SLR (n = 49)
|
P-value
|
Age [year]
|
75(47-88)
|
65(31-83)
|
<0.001
|
67(47-84)
|
68(46-83)
|
0.727
|
Gender (Male: Female)
|
60:26
|
41:38
|
0.019
|
33:16
|
33:16
|
1.000
|
PS (0:1:2)
|
13:70:3
|
48:30:1
|
<0.001
|
13:36:0
|
22:26:1
|
0.085
|
FEV1 [L]
|
1.48(0.48-3.27)
|
1.80(0.78-3.90)
|
<0.001
|
1.61(0.48-3.27)
|
1.57(0.78-2.98)
|
0.534
|
Tumor diameter [mm]
|
22(7-47)
|
17(5-45)
|
0.007
|
22(7-45)
|
20(8-45)
|
0.730
|
Stage (IA: IB)
|
70:16
|
69:10
|
0.295
|
40:9
|
39:10
|
0.798
|
Histology
|
|
|
<0.001
|
|
|
0.030
|
Sq
|
25
|
18
|
|
15
|
12
|
|
Ad
|
38
|
58
|
|
23
|
34
|
|
Other
|
23
|
3
|
|
11
|
3
|
|
Prior lobectomies
|
8
|
12
|
0.247
|
6
|
8
|
0.564
|
CCI
|
2(0-6)
|
2(0-5)
|
0.144
|
1(0-6)
|
2(0-4)
|
0.058
|
PET/CT
|
56
|
13
|
<0.001
|
30
|
9
|
<0.001
|
Abbreviations: SBRT, stereotactic body radiotherapy; SLR, sublobar resection; PS, performance status; FEV1, forced expiratory volume in 1 second; Sq, squamous cell carcinomas; Ad, adenocarcinomas; CCI, Charlson Comorbidity Index;PET/CT, positron emission tomography/computed tomography.
Values are shown in median (range) for continuous data.
A propensity score analysis was performed in SBRT and SLR groups. 49 patients were identified from each group, and no difference in terms of age, gender, PS, tumor size, FEV1 and cancer stage was found between matched SBRT and SLR patients (Table 1). The prior lobectomies did not show significant difference (6 and 8 patients, respectively, P = 0.564). FDG-PET/CT was performed in 30 (61.2%) SBRT patients, compared with 9 (18.4%) SLR patients (P < 0.001). 26 SLR patients underwent segmentectomy, and the rest 23 received wedge resection. Lymph-node systematic dissection or sampling was performed in 22 (84.6%) and 4 (17.4%) patients, respectively. The additional 4 and 19 patients did not undergo lymph node dissection, as no detectable lymph node was shown on preoperative CT/PET-CT examination or found during the surgery. VATS was performed in 41 (83.7%) SLR patients, among whom, 2 (4.1%) patients also had to take thoracotomy. 8 (16.3%) patients remained underwent SLR by taking thoracotomy. 2 (4.1%) patients had positive surgical margin after wedge resection, specifically, one patient with positive surgical margin did not have intraoperative frozen section analysis, while the operation in another patient was forced to complete due to a drop in oxygen saturation and blood pressure. SBRT patients mainly treated with 50Gy prescribed dose (prescribed to the PTV margin) in 5 fractions, and the biological effective dose (BED) was 100Gy (α/β=10). The dose segmentation scheme was adjusted according to lung function, comorbidities and life expectancy.
Survival and Recurrence Differences
Prior to perform PSM, the median follow-up periods of SBRT and SLR groups were 32 and 37 months, respectively. The median overall survival in each group was not reached at the time of last follow-up. 21 SBRT and 16 SLR patients died during follow-up, among them, 34 patients died of lung cancer, while 3 died of other causes. One case of treatment-related death occurred after SLR due to cardiac tamponade. One SLR patient died of a fracture 6.87 months after receiving segmentectomy, whereas one SBRT patient died of pneumonia 2 months after taking radiotherapy. No significant differences in OS (80.3% and 82.3% for 3-year OS, P = 0.405) (Figure 1a) and CSS (81.3% and 83.4% for 3-years CCS, P = 0.383) (Figure 1b) were found.
At the time of the last follow-up, 28 SBRT and 25 SLR patients experienced disease recurrence, and difference in recurrence-free survival was not significant (62.4%, and 69.9% for 3-year recurrence-free survival, P = 0.383) between the 2 groups. In SBRT and SLR groups, 8 and 11 cases of local recurrence, 10 and 10 cases of regional recurrence and 22 and 21 cases of distant recurrence were observed, respectively. The rates of local (Figure 2), regional and distance control did not have significant difference (89.7% and 86.0% for 3-years local control, P = 0.501; 87.1% and 87.9% for 3-year regional control, P = 0.884 and 71.6% and 74.4% for 3-year distance control, P = 0.662, respectively).
After performing PSM, 10 patients treated by SBRT and 13 patients treated by SLR died before the last follow-up, among them, 9 SBRT and 11 SLR patients were died of lung cancer recurrence, while 3 died of other causes. No statistically significant difference was identified in OS (85.4% and 73.3% for 3-year OS, P = 0.649) (Figure 3a) and cause-specific survival (CSS) (87.2% and 74.9% for 3-years CCS, P = 0.637) (Figure 3b) between the matched SBRT and SLR groups.
14 SBRT and 19 SLR patients in the matched groups experienced disease recurrence, and the difference in recurrence-free survival was not significant (66.7%, and 63.2% for 3-year RFS, P = 0.689) between the 2 matched groups. In the matched SBRT and SLR groups, 2 and 9 cases of local recurrence, 4 and 8 cases of regional recurrence and 11 and 16 cases of distant recurrence were identified, respectively. The rates of local (Figure 4), regional and distance control did not show significant difference (95.6% and 82.1% for 3-year local control, P = 0.055; 91.4% and 85.2% for 3-year regional control, P = 0.432 and 73.7% and 68.3% for 3-year distance control, P = 0.548, respectively).
In a subgroup analysis of matched patients, the number of patients was limited in wedge resection and segmentectomy subgroup. No significant difference was identified in OS, CSS, recurrence-free survival, regional control and distance control between SBRT and segmentectomy or between SBRT and wedge resection (P > 0.05). Local control of SBRT patients was better than those received wedge resection (95.6% versus 67.4% for 3-year local control, P = 0.005). The patients treated with segmentectomy had a tendency of improved 3-year local control (95.7% versus 67.4%; P = 0.075) and recurrence-free survival (77.2% versus 49.3%, P = 0.076), compared with those underwent wedge resection. However, the patients who had wedge resection had a higher CCI, compared with those received segmentectomy (P = 0.013).
Treatment toxicity
Posttreatment adverse events in the matched SBRT and SLR patients are shown in Table 2. In the SBRT cohort, 7 (14.3%) patients experienced grade 2 respiratory adverse events, specifically, there were 6 cases (12.2%) of radiation pneumonitis and 1 case (2.0%) of cough, which were all respiratory complications, however, no other grade 3 or worse adverse events was observed. In the SLR cohort, 13 patients (26.5%) had grade 2 or worse adverse events, while 8 patients (16.3%), which included 5 cases (10.2%) of dyspnea and 3 cases (6.1%) of chest wall pain, experienced grade 2 adverse events. Grade 3, 4 and 5 adverse events occurred to 5 patients (10.2%), including 2 cases (4.1%) of atrial fibrillation, 1 case (2.0%) of pulmonary thromboembolism, 1 case of (2.0%) of hypoxia and 1 case (2.0%) of pericardial tamponade. Grade 3 or worse adverse events after SLR were frequently cardiovascular diseases. The rate of grade 3 or worse adverse events was 0 and 10.2% in matched SBRT and SLR groups, respectively (P = 0.056).