An investigative expansion of a competing risk model for first failure site in locally advanced non-small cell lung cancer

Figures & data

Table 1. Patient and treatment characteristics by histopathologic subtype.

Characteristic	Total (n = 342)	%	AC, n (%)	SCC, n (%)	p-value
Median age at diagnosis, y (range)	66 (37–89)		64 (37–89)	67 (43–89)	.37
UICC clinical stage					.15
I	5	1.5	4 (2.0%)	1 (0.7%)
II	38	11.1	20 (9.8%)	18 (13.1%)
IIIA/IIIB	272	79.5	160 (78.0%)	112 (81.8%)
IV	27	7.9	21 (10.2%)	6 (4.4%)
Tumor stage (surgery^a)					.004
TX	3	0.9	1 (0.5%)	2 (1.5%)
T1 (8)	43	12.6	35 (17.1%)	8 (5.8%)
T2 (8)	81	23.7	49 (23.9%)	32 (23.4%)
T3 (5)	77	22.5	51 (24.9%)	26 (19.0%)
T4 (3)	138	40.4	69 (33.7%)	69 (50.4%)
Nodal stage					.027
N0	71	20.8	39 (19.0%)	32 (23.4%)
N1	34	9.9	16 (7.8%)	18 (13.1%)
N2	170	49.7	100 (48.8%)	70 (51.1%)
N3	67	19.6	50 (24.4%)	17 (12.4%)
Sex					.20
Male	198	57.9	113 (55.1%)	85 (62.1%)
Female	144	42.1	92 (44.9%)	52 (37.9%)
Histopathologic type
AC	205	59.1	205	–
SCC	137	40.1	–	137
WHO performance status					.12
0	202	59.1	123 (60.0%)	79 (57.7%)
1	127	37.1	71 (34.6%)	56 (40.9%)
2	13	3.8	11 (5.4%)	2 (1.4%)
Chemotherapy regimen					.37
Cisplatin/vinorelbine	197	57.6	123 (60%)	74 (54.0%)
Carboplatin/vinorelbine	119	34.8	66 (32.2%)	53 (38.7%)
No chemotherapy	25	7.3	16 (7.8%)	9 (6.6%)
No data available	1	0.3		1 (0.7%)
Concomitant	243	76.9	147 (77.8%)	96 (75.6%)	.60
Sequential	73	23.1	42 (22.2%)	31 (24.4%)
Radiation DOSE					.56
2 Gy × 30 (total 60 Gy)	9	2.6	5 (2.4%)	4 (3.0%)
2 Gy × 33 (total 66 Gy)	330	96.5	197 (96.1%)	133 (97.0%)
Did not complete (<50 Gy)	2	0.6	2 (1.0%)
Reduced dose (62.5 Gy)	1	0.3	1 (0.5%)
Target characteristics	AC, Median (range)		SCC, Median (range)		p-value
GTV
Tumor	85.0 (0.6–791.7)		118.1 (2.2–664.5)		.55
Nodal	25.2 (0.4–308.9)		17.5 (0.4–155)		.32
Total	99.0 (0.6–804.5)		126.2 (3.4–665.5)		.47
SUVpeak, T-Site^b	12.6 (1.00–58.8)		13.0 (2.6–43.3)		.75
SUVpeak, N-Site^b	9.6 (0.9–38.6)		8.6 (1.3–28.8)		.58

Categorical variables (clinical stage, T-stage, N-stage, sex, performance status, chemotherapy regimen and radiation dose) were analyzed by chi-squared method. Nonparametric variables (age and target characteristics) were analyzed by the Mann–Whitney U test. Significant p-values (p < .05) are highlighted in boldface.

^a27 patients without SUV-uptake in T-site; 24 had video-assisted thoracic surgery, 3 had no primary tumor. Patients who underwent surgery prior to definitive radiotherapy are listed with T-stage prior to surgery.

^bThe highest value of SUV_peak was chosen in cases of multiple T-site or N-site lesions.

AC: adenocarcinoma; SCC: squamous cell carcinoma; UICC: Union for International Cancer Control: 7th version; GTV: gross tumor volume; SUV: standardized uptake value; SUV_peak: peak standardized uptake value; T-site: tumor site; N-site: lymph nodes.

Table 2. Subdistribution of hazard ratios in competing risk models: locoregional failure or distant metastases as first site of failure.

Covariable	Unit	HR (95% CI), p Value; Simplified model without volumetrics	HR (95% CI), p Value; Expanded model with separated GTV
Outcome 1: Locoregional relapse as first site of failure
Histopathology	SCC (ref)
	AC	0.49 (0.31–0.75) p = .001	0.5 (0.32–0.78) p = .002
PS	≥1 vs. 0	1.73 (1.12–2.67) p = .014	1.69 (1.09–2.61) p = .019
Clinical Stage	III vs. I and II	1.53 (0.76–3.06) p = .234	1.42 (0.70–2.88) p = .337
	IV vs. I and II	0.92 (0.25–3.41) p = .899	0.93 (0.25–3.46) p = .917
GTV	Per 50 cm^3 increase
GTVT			1.06 (0.95–1.18) p = .268
GTVN			1.18 (0.81–1.71) p = .388
SUVpeak, T-sites	Per 10 unit increase		1.04 (0.76–1.44) p = .791
SUVpeak, N-sites	Per 10 unit increase		0.93 (0.60–1.43) p = .739
Outcome 2: Distant metastases as first site of failure
Histopathology	SCC (ref)
	AC	2.08 (1.45–2.98) p<.001	2.08 (1.44–3.01) p<.001
PS	≥1 vs. 0	0.88 (0.64–1.22) p = .459	0.87 (0.63–1.21) p = .424
Clinical Stage	III vs. I and II	1.76 (1.01–3.07) p = .045	1.54 (0.88–2.70) p = .134
	IV vs. I and II	3.14 (1.58–6.24) p = .001	3.22 (1.62–6.42) p<.001
GTV	Per 50 cm^3 increase
GTVT			1.07 (0.99–1.16) p = .087
GTVN			0.97 (0.76–1.26) p = .843
SUVpeak, N-sites	Per 10 unit increase		1.44 (1.15–1.79) p = .001
Outcome 3: Dead with NED as first event
Age	Years	1.01 (0.98–1.05) p = .446	1.01 (0.98–1.05) p = .446
PS	≥1 vs. 0	1.56 (0.84–2.90) p = .157	1.56 (0.84–2.90) p = .157

Locoregional failure or Distant Metastases as first site of failure. Dead with NED as first event. Significant p-values (<.05) are highlighted in boldface.

HR: hazard ratio; CI: confidence interval; GTV: gross tumor volume; SUV_peak: peak of standardized uptake value; AC: adenocarcinoma; SCC: squamous cell carcinoma; PS: performance status; T-sites: tumor sites; N-sites: lymph nodes; NED: no evidence of disease

Figure 1. Comparison of tumor volumes across histopathologic subtypes. GTV_T: gross tumor volume of T-site; GTV_N: gross tumor volume of N-site; SCC: squamous cell carcinoma; AC: adenocarcinoma.

Figure 2. First failure site by histopathologic subtype. Cumulative incidence rates of outcome variables by histopathology subtype. AC: adenocarcinoma; SCC: squamous cell carcinoma; DM: distant metastasis; NED: no evidence of disease.