Impact Of Underlying Pulmonary Diseases On Treatment Outcomes In Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiotherapy

Figures & data

Table 1 Clinical Characteristics Of Patients Treated With Definitive Radiotherapy For Early Stage NSCLC (N = 234)

Characteristics	Control* (n=64)	COPD (n=132)	CPFE (n=16)	IPF (n=22)	P Value
Age (years)	78.5 (74.0–81.5)	75.0 (71.0–79.0)	76.0 (74.0–79.0)	74.5 (72.0–79.0)	0.036
Sex  Female  Male	30 (46.9%) 34 (53.1%)	15 (11.4%) 117 (88.6%)	0 (0%) 16 (100%)	0 (0%) 22 (100%)	<0.001
Smoking Status  Never smoker  Current or Ex-smoker  Pack-years^†	34 (53.1%) 30 (46.9%) 45 (30–60)	15 (11.4%) 117 (88.6%) 40 (30–55)	0 (0%) 16 (100%) 40 (25–50)	0 (0%) 22 (100%) 40 (30–59)	<0.001
ECOG performance status  0–1  2–3	45 (70.3%) 19 (29.7%)	92 (69.7%) 40 (30.3%)	9 (56.3%) 7 (43.7%)	13 (59.1%) 9 (40.9%)	0.542
Clinical Stage  IA-IB  IIA-IIB	48 (75.0%) 16 (25.0%)	96 (72.7%) 36 (27.3%)	11 (68.8%) 5 (31.2%)	15 (68.2%) 7 (31.8%)	0.914
Histology  Adenocarcinoma  Squamous cell carcinoma  Others  Not proven	28 (43.8%) 21 (32.8%) 4 (6.3%) 11 (17.1%)	31 (23.5%) 75 (56.8%) 7 (5.3%) 19 (14.4%)	2 (12.5%) 7 (43.8%) 1 (6.3%) 6 (37.4%)	5 (22.7%) 10 (45.5%) 1 (4.5%) 6 (27.3%)	0.02
Pulmonary Function Test
FVC, L	2.6 (2.1–3.0)	3.0 (2.5–3.5)	3.4 (3.1–3.8)	3.1 (2.9–3.8)	<0.001
FVC, % pred	82.0 (71.5–92.5)	80.5 (67.5–90.5)	88.0 (78.5–94.0)	83.0 (74.0–89.0)	0.284
FEV1, L	2.0 (1.6–2.4)	1.5 (1.2–1.9)	2.2 (2.0–2.5)	2.2 (2.1–2.6)	<0.001
FEV1, % pred	95.5 (80.5–112.0)	64.0 (46.0–75.5)	82.0 (75.0–102.0)	85.5 (80.0–97.0)	<0.001
FEV1/FVC, %	77.0 (74.0–81.5)	55.0 (44.0–63.0)	63.0 (60.0–73.5)	71.5 (67.0–76.0)	<0.001
DLco, % pred‡	80.0 (68.0–93.0)	67.0 (54.5–87.0)	55.0 (45.0–65.0)	56.0 (44.0–66.5)	<0.001
FEV1 ≤ 80% pred	16 (25.0%)	107 (81.1%)	5 (31.3%)	6 (27.3%)	<0.001
FEV1 ≤ 50% pred	1 (1.6%)	45 (34.1%)	1 (6.2%)	1 (4.5%)	<0.001
DLco ≤ 80% pred‡	27 (50.9%)	77 (66.4%)	13 (86.7%)	19 (95.0%)	<0.001
DLco ≤ 60% pred‡	7 (13.2%)	42 (36.2%)	11 (73.3%)	13 (65.0%)	<0.001
Radiotherapy technique  3DCRT/IMRT  SBRT	37 (57.8%) 27 (42.2%)	85 (64.4%) 47 (35.6%)	7 (43.8%) 9 (56.2%)	14 (63.6%) 8 (36.4%)	0.395
Radiotherapy planning parameters for total lung volume  Mean dose (cGy)  V5 (%)  V20 (%)	836.0 (544.4–1104.9) 27.0 (20.9–36.5) 14.7 (9.1–20.4)	769.6 (560.2–1052.3) 29.1 (22.7–36.8) 13.6 (9.5–18.5)	632.6 (498.3–1007.3) 27.2 (19.3–33.3) 11.5 (7.9–18.0)	708.1 (608.9–987.6) 27.9 (25.1–33.2) 11.9 (9.0–18.2)	0.714 0.822 0.249

Notes: Data are presented as number (%) or median (interquartile range). *Non-COPD, non-CPFE, and non-IPF. ^†Pack-year was calculated among 185 current or ex-smokers. ^‡DLco was available in 204 patients.

Abbreviations: 3DCRT, 3-dimensional conformal radiation therapy; COPD, chronic obstructive pulmonary disease; CPFE, combined pulmonary fibrosis and emphysema; ECOG, Eastern Cooperative Oncology Group; DL_CO, diffusing capacity of the lung for carbon monoxide; FEV_1, forced expiratory volume in 1 second; IMRT, intensity-modulated radiation therapy; IPF, idiopathic pulmonary fibrosis; NSCLC, non-small cell lung cancer; SBRT, stereotactic body radiation therapy; V_D, percentage volume of organ receiving ≥ D Gy.

Table 2 Cox Proportional Hazard Analysis For Factors Associated With Overall Survival (N=234)

Characteristics	Hazard Ratio	95% CI	P Value
Crude
Control	Reference
COPD	0.927	0.564–1.524	0.765
CPFE	2.853	1.343–6.062	0.006
IPF	4.344	2.301–8.201	<0.001
Model 1
Control	Reference
COPD	1.326	0.725–2.425	0.360
CPFE	3.034	1.328–6.931	0.009
IPF	4.246	2.060–8.753	<0.001
Model 2
Control	Reference
COPD	1.306	0.723–2.358	0.376
CPFE	3.382	1.472–7.769	0.004
IPF	4.061	1.963–8.403	<0.001

Notes: Model 1 adjusted for age, smoking status, performance status (ECOG ≤ 1 or ≥ 2), clinical stage (clinical stage I or II), FEV₁≤ 80% pred and DLco≤ 60% pred. Model 2 adjusted for age, smoking status, performance status (ECOG ≤ 1 or ≥ 2), clinical stage (clinical stage I or II), FEV₁≤ 80% pred, DLco≤ 60% pred and Radiotherapy technique.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; CPFE, combined pulmonary fibrosis and emphysema; IPF, idiopathic pulmonary fibrosis.

Table 3 Radiation Pneumonitis According To Underlying Pulmonary Diseases (N=234)

Characteristics	Control*	COPD	CPFE	IPF	P value
All patients (N=234)	64	132	16	22
≥ Grade 3 RP	1 (1.6%)	3 (2.3%)	1 (6.3%)	7 (31.8%)	<0.001
Subgroup analysis with stage I NSCLC (N=170)	48	96	11	15
≥ Grade 3 RP	0 (0.0%)	2 (2.1%)	1 (9.1%)	4 (26.7%)	<0.001
Subgroup analysis with stage II NSCLC (N=64)	16	36	5	7
≥ Grade 3 RP	1 (6.3%)	1 (2.8%)	0 (0.0%)	3 (42.9%)	0.003

Notes: Data are presented as n or number (%). *Non-COPD, non-CPFE, and non-IPF.

Abbreviations: COPD, chronic obstructive pulmonary disease; CPFE, combined pulmonary fibrosis and emphysema; IPF, idiopathic pulmonary fibrosis; RP, radiation pneumonitis.

Figure 1 Overall survival curves according to underlying pulmonary diseases in patients treated with definitive radiotherapy alone.

Figure 2 Overall survival curves according to underlying pulmonary diseases in subgroup analysis according to clinical stages; stage I (A) and II (B).