Radiotherapy for patients with stage IV classical Hodgkin lymphoma: a propensity-matched analysis of the surveillance, epidemiology, and end results database

Figures & data

Figure 1. The flowchart of study population selection.

Table 1. Baseline characteristics of patients with stage IV HL, before and after PSM, SEER 2000–2012.

	Before PSM^1 (N = 3197)				After PSM^1 (N = 1829)
Variable	N	No-RT^2	RT	P^3	N	No-RT	RT	P^3
Age [Years, mean (SD)] <45 (%) ≧45 (%)	2123 1074	40.5 (17.9) 73.8 89.7	28.3 (16.1) 26.2 10.3	<0.001 <0.001	1488 341	31.6 (15.7) 62.6 67.4	28.3 (16.1) 37.4 32.6	<0.001 0.096
Gender(%) Male Female	1931 1266	80.1 77.7	19.9 22.3	0.112	1061 768	63.7 63.3	36.3 35.7	0.850
Race (%) White Others	2487 710	79.0 79.7	21.0 20.3	0.665	1403 426	62.7 66.2	37.3 33.8	0.192
Marital status (%) Married Unmarried	1466 1731	84.3 74.8	15.7 25.2	<0.001	625 1204	63.2 63.7	36.8 36.3	0.832
CHSDA Region (%) Pacific Coast/Alaska East Northern Plains Southwest	1537 1252 251 157	77.6 81.7 74.5 81.5	22.4 18.3 25.5 18.5	0.011	900 696 147 86	61.7 67.1 56.5 66.3	38.3 32.9 43.5 33.7	0.035
Income (%) <5000 ≧5000	1387 1810	79.6 78.8	20.4 21.2	0.576	800 1029	64.6 62.7	35.4 37.3	0.392
Lymphoma subtype (%) Nodular sclerosis Lymphocyte-rich Mixed cellularity Lymphocyte-depleted Classical HL, NOS	1861 56 397 63 820	73.6 82.1 87.7 85.7 86.8	26.4 17.9 12.3 14.3 13.2	<0.001	1192 27 190 34 386	58.8 63.0 74.2 73.5 72.0	58.8 37.0 25.8 26.5 28.0	<0.001
B symptoms (%) No Yes Unknown	687 1502 1008	75.4 83.1 75.8	24.6 16.9 24.2	<0.001	454 749 626	62.8 66.1 61.0	37.2 33.9 39.0	0.140
Extra nodal involvement (%) No Yes	3126 71	79.0 83.1	21.0 16.9	0.406	1793 36	63.5 66.7	36.5 33.3	0.693
Chemotherapy (%) No/unknown Yes	223 2974	92.8 78.1	7.2 21.9	<0.001	95 1734	83.2 62.5	16.8 37.5	<0.001
Surgery (%) No Yes	1969 1228	80.8 76	19.2 23.5	0.0044	1103 726	65.6 60.3	34.4 39.7	0.021

Abbreviations: HL, Hodgkin lymphoma; SEER, Surveillance, Epidemiology, and End Results; N, number of cases; PSM, propensity score matching; RT, radiotherapy; CHSDA, Contract Health Services Delivery Areas; NOS, not otherwise specified.

¹Selected covariates for Propensity score analysis with 1:2 matching were age (divided by four equal), income, and the presence of B symptoms.

²”No-RT” means patients who did not receive radiotherapy.

³Derived from Mann-Whitney U test for continuous variables and X² test for categorical variables.

Table 2. Univariate analysis of OS and CSS in patients with stage IV HL who received chemotherapy, before PSM, SEER 2000–2012.

		OS			CSS
Variable	N	5-year CSS rate (%)	Mean (months, 95% CI)	P^1	5-year CSS rate (%)	Mean (months, 95% CI)	P^1
Age <45 ≧45	2006 968	89.8 75.6	147.5 (145.2–149.8) 119.3 (114.7–123.8)	<0.001	91.8 82.4	152.4 (150.3–154.4) 136.4 (132.2–140.5)	<0.001
Gender Male Female	1782 1192	84.5 86.3	137.0 (134.1–139.9) 140.7 (137.3–144.0)	0.129	87.7 90.3	146.2 (143.6–148.7) 149.1 (146.2–152.1)	0.106
Race White Others	2312 662	85.2 85.4	138.4 (135.9–140.9) 138.7 (134.0–143.4)	0.822	89.0 88.1	147.9 (145.8–150.1) 145.3 (141.1–149.7)	0.380
Marital status Married Unmarried	1339 1635	81.7 88.2	131.6 (128.2–135.1) 144.4 (141.7–147.2)	<0.001	86.3 90.8	143.6 (140.5–146.6) 150.6 (148.2–153.0)	<0.001
CHSDA Region Pacific Coast/Alaska East Northern Plains Southwest	1459 1140 232 143	85.7 85.3 83.4 82.3	140.0 (137.0–143.1) 138.8 (135.3–142.3) 131.1 (122.3–140.0) 129.4 (118.5–140.4)	0.179 0.666 0.129 0.076	89.2 89.2 86.3 85.0	148.1 (145.5–150.8) 148.5 (145.5–151.5) 138.3 (130.1–146.5) 141.0 (131.2–150.9)	0.128 0.844 0.068 0.150
Income <5000 ≧5000	1273 1701	82.6 87.2	134.4 (130.9–138.0) 141.5 (138.7–144.3)	0.001	87.2 90.0	144.7 (141.5–147.8) 149.4 (147.0–151.8)	0.016
Lymphoma subtype Nodular sclerosis Lymphocyte-rich Mixed cellularity Lymphocyte-depleted Classical HL NOS	1747 50 372 57 748	1747 80.2 82.9 78.6 81.8	143.6 (141.0–146.2) 135.3 (116.7–153.9) 132.8 (126.2–139.4) 124.3 (108.9–139.7) 129.7 (124.8–140.7)	<0.001 0.297 0.001 0.034 <0.001	80.2 86.8 84.3 90.0 87.8	140.6 (124.0–157.2) 142.2 (136.2–148.2) 133.8 (120.0–147.7) 150.3 (148.0–152.6) 143.9 (139.6–148.2)	0.008 0.128 0.008 0.074 0.007
B symptoms No Yes Unknown	641 1430 903	90.4 84.7 83.0	108.1 (105.6–110.6) 102.1 (100.1–104.1) 136.1 (132.5–139.7)	0.001 0.001 <0.001	92.8 89.2 85.9	111.7 (109.6–113.8) 107.1 (105.3–108.8) 144.3 (140.9–147.6)	0.001 0.003 <0.001
Extra nodal involvement No Yes	2909 65	85.2 86.8	138.4 (136.1–140.6) 140.5 (127.5–153.7)	0.458	88.7 93.3	147.2 (145.2–149.1) 152.8 (144.0–161.5)	0.161
Surgery No Yes	1830 1144	85.2 85.4	137.8 (134.8–140.8) 139.3 (136.0–142.6)	0.544	89.4 88.0	147.6 (145.0–150.2) 147.0 (144.1–150.0)	0.666
Radiotherapy No Yes	2323 651	83.4 91.5	134.9 (132.3–137.6) 150.0 (146.3–153.6)	<0.001	87.7 92.5	145.2 (142.9–147.5) 154.2 (150.9–157.4)	<0.001

Abbreviations:HL, Hodgkin lymphoma; SEER, Surveillance, Epidemiology, and End Results; N, number of cases; PSM, propensity score matching; OS, overall survival; CSS, cancer-specific survival; CHSDA, Contract Health Services Delivery Areas; NOS, not otherwise specified.

¹Derived from Kaplan-Meier survival analysis.

Figure 2. (2a) Kaplan-Meier survival curve of OS in patients with stage IV HL after PSM. (2b) Kaplan-Meier survival curve of CSS in patients with stage IV HL after PSM. (2c) Kaplan-Meier survival curve of OS in stage IV HL patients without B symptoms after PSM. (2d) Kaplan-Meier survival curve of OS in stage IV HL patients with B symptoms after PSM.

Abbreviations: OS, overall survival; CSS, cancer-specific survival; PSM, propensity score matching; RT, radiotherapy; HL, Hodgkin lymphoma.*Entered in PSM were variables including age group (divided by four equal), income level, and the presence of B symptoms. Note: Confidence intervals were not present for clarity of the figure.

Table 3. Multivariate analysis of OS and CSS in patients with stage IV HL who received chemotherapy, after PSM,¹ SEER 2000–2012.

	OS		CSS
Variable	HR (95% CI)	P^2	HR (95% CI)	P^2
Age <45 (as ref) ≧45	1.00 2.71 (2.09–3.52)	<0.001	1.00 2.57 (1.89–3.49)	<0.001
Income (%) <5000 (as ref.) ≧5000	1.00 0.77 (0.60–0.98)	0.036	1.00 0.79 (0.59–1.05)	0.108
B symptoms No (as ref.) Yes Unknown	1.00 1.95 (1.31–2.90) 1.69 (1.13–2.53)	0.001 0.010	1.00 2.37 (1.45–3.87) 2.27 (1.39–3.72)	0.001 0.001
Radiotherapy No (as ref.) Yes	1.00 0.68 (0.51–0.89)	0.006	1.00 0.69 (0.50–0.95)	0.022

Abbreviations: OS, overall survival; CSS, cancer-specific survival; HL, Hodgkin lymphoma; SEER, Surveillance, Epidemiology, and End Results; PSM, propensity score matching; HR, hazard ratio; CI, confidence interval.

¹Selected covariates for Propensity score analysis with 1:2 matching were age (divided by four equal), income, and the presence of B symptoms.

²Derived from multivariate Cox proportional-hazards models. Present here is the final model. Insignificant variables were dropped, and variables remained in the final model were age group (<45,≧45), family income level, presence of B symptoms, and radiotherapy.

Table 4. Effect of radiotherapy on OS and CSS by different subgroups in patients with stage IV HL, after PSM, SEER 2000–2012.

			OS (months)			CSS (months)
Variable	N with RT (%)	N without RT(%)	HR for RT(95% CI)	p^#	p*	HR for RT(95% CI)	p^#	p*
Age <45 ≧45	548 (38.6) 103 (32.6)	870 (61.4) 213 (67.4)	0.61 (0.44–0.86) 0.74 (0.46–1.20)	0.004 0.216	0.727	0.62 (0.42–0.92) 0.86 (0.50–1.50)	0.016 0.604	0.541
Income <5000 ≧5000	272 (36.4) 379 (38.4)	475 (63.6) 608 (61.6)	0.57 (0.38–0.87) 0.74 (0.51–1.07)	0.009 0.109	0.299	0.55 (0.33–0.90) 0.83 (0.54–1.26)	0.018 0.372	0.162
B symptoms No Yes	166 (38.3) 251 (34.5)	267 (61.7) 476 (65.5)	0.35 (0.14–0.85) 0.75 (0.49–1.14)	0.021 0.184	0.099	0.50 (0.18–1.39) 0.86 (0.54–1.39)	0.183 0.548	0.255

Abbreviations: OS, overall survival; CSS, cancer-specific survival; HL, Hodgkin lymphoma; SEER, Surveillance, Epidemiology, and End Results; PSM, propensity score matching; N, number of cases; RT, radiotherapy; HR, hazard ratio; CI, confidence interval.

P^# for multivariate analysis of RT within each subgroup. Derived from Cox proportional-hazards models.

P* for interaction between subgroups. Derived from multivariate Cox proportional-hazards models. Patients with unknown status of B symptoms were excluded.

The result presented here is from the final model. Variables selected in the final model were age group (<45, ≧45), family income level and presence of B symptoms.