Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma

Table 1 Baseline demographic and clinical characteristics of elderly patients with pancreatic ductal adenocarcinoma between 2004 and 2018 from Surveillance, Epidemiology, and End Results database before and after propensity score matching

Variables	Subgroups	Before propensity score matching, n (%) of patients (n = 12245)			After propensity score matching, n (%) of patients (n = 4500)
		RT	Non-RT	P value	RT	Non-RT	P value
All parents		9694 (79.2)	2551 (20.8)		2250 (50)	2250 (50)
Age (yr)	65-80	2160 (84.7)	7423 (76.6)	< 0.001	1884 (83.7)	1857 (82.5)	0.301
	> 80	391 (15.3)	2271 (23.4)		366 (16.3)	393 (17.5)
Year of diagnosis	2004-2010	1329 (52.1)	5195 (53.6)	0.186	1185 (52.7)	1184 (52.6)	1.00
	2011-2018	1222 (47.9)	4499 (46.4)		1065 (47.3)	1066 (47.4)
Sex	Female	1166 (45.7)	3203 (33.0)	< 0.001	898 (39.9)	875 (38.9)	0.502
	Male	1385 (54.3)	6491 (67.0)		1352 (60.1)	1375 (61.1)
Race	White	2021 (79.2)	7687 (79.3)	0.713	1784 (79.3)	1789 (79.5)	0.916
	Black	249 (9.8)	983 (10.1)		218 (9.7)	210 (9.3)
	Other	281 (11.0)	1024 (10.6)		248 (11.0)	251 (11.2)
Marital status	Married	1586 (62.2)	5384 (55.5)	< 0.001	1377 (61.2)	1359 (60.4)	0.604
	Unmarried	965 (37.8)	4310 (44.5)		873 (38.8)	891 (39.6)
Primary site	Head	1737 (68.1)	5414 (55.8)	< 0.001	1509 (67.1)	1536 (68.3)	0.635
	Body/tail	503 (19.7)	2739 (28.3)		452 (20.1)	428 (19.0)
	Other	311 (12.2)	1541 (15.9)		289 (12.8)	286 (12.7)
Histology grade	Grade I-II	692 (27.1)	1882 (19.4)	< 0.001	579 (25.7)	578 (25.7)	0.952
	Grade III-IV	472 (18.5)	1344 (13.9)		406 (18.0)	414 (18.4)
	Unknow	1387 (54.4)	6468 (66.7)		1265 (56.2)	1258 (55.9)
Node status	Negative	1457 (57.1)	6047 (62.4)	< 0.001	1295 (57.6)	1328 (59.0)	0.333
	Positive	1094 (42.9)	3647 (37.6)		955 (42.4)	922 (41.0)
Tumor size (cm)	< 2	229 (9.0)	909 (9.4)	< 0.001	195 (8.7)	207 (9.2)	0.821
	2-4	1491 (58.4)	5076 (52.4)		1317 (58.5)	1310 (58.2)
	> 4	831 (32.6)	3709 (38.3)		738 (32.8)	733 (32.6)
SEER stage	Localized	320 (12.5)	1019 (10.5)	< 0.001	285 (12.7)	306 (13.6)	0.606
	Regional	1813 (71.1)	3726 (38.4)		1547 (68.8)	1540 (68.4)
	Distant	418 (16.4%)	4949 (51.1)		418 (18.6)	404 (18.0)
Surgery	No	1592 (62.4)	7622 (78.6)	< 0.001	1439 (64.0)	1466 (65.2)	0.418
	Yes	959 (37.6)	2072 (21.4)		811 (36.0)	784 (34.8)
Chemotherapy	No	297 (11.6)	4304 (44.4)	< 0.001	297 (13.2)	310 (13.8)	0.601
	Yes	2254 (88.4)	5390 (55.6)		1953 (86.8)	1940 (86.2)

RT: Radiation therapy; SEER: Surveillance, Epidemiology, and End Results.

Table 2 Logistic regression model of factors associated with receiving radiation in elderly patients with pancreatic ductal adenocarcinoma between 2004 and 2018 from Surveillance, Epidemiology, and End Results database

Variables	Subgroups	Odds ratio (95%CI)	P value
Age (yr)	65-80	Reference
	> 80	0.84 (0.74-0.97)	0.014
Year of diagnosis	2004-2010	Reference
	2011-2018	0.47 (0.42-0.52)	< 0.001
Sex	Female	Reference
	Male	1.01 (0.91-1.11)	0.909
Race	White	Reference
	Black	1.1(0.93-1.3)	0.25
	Other	0.90 (0.77-1.05)	0.19
Marital status	Married	Reference
	Unmarried	0.92 (0.83-1.03)	0.144
Primary site	Head	Reference
	Body/tail	0.87 (0.77-0.99)	0.032
	Other	0.85 (0.73-0.98)	0.031
Histology grade	Grade I-II	Reference
	Grade III-IV	0.95(0.82-1.11)	0.55
	Unknow	1(0.87-1.16)	0.948
Node status	Negative	Reference
	Positive	0.99 (0.89-1.11)	0.864
Tumor size (cm)	< 2	Reference
	2-4	1.24 (1.04-1.48)	0.016
	> 4	1.23 (1.02-1.48)	0.033
SEER stage	Localized	Reference
	Regional	1.01 (0.86-1.19)	0.891
	Distant	0.17 (0.14-0.21)	< 0.001
Surgery	No	Reference
	Yes	1.02 (0.88-1.17)	0.804
Chemotherapy	No	Reference
	Yes	7.05 (6.14-8.1)	< 0.001

SEER: Surveillance, Epidemiology, and End Results; CI: Confidence interval.

Table 3 Cox proportional hazards regression for overall survival and cancer-specific survival of elderly patients with pancreatic ductal adenocarcinoma between 2004 and 2018 from Surveillance, Epidemiology, and End Results database after propensity score matching

Variables	Subgroups	Overall survival				Cancer-specific survival
		Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
		HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age (yr)	65-80	Reference		Reference		Reference		Reference
	> 80	1.486 (1.367-1.615)	< 0.001	0.966 (0.852-1.095)	0.588	1.473 (1.352-1.605)	< 0.001	0.953 (0.838-1.084)	0.466
Year of diagnosis	2004-2010	Reference		Reference		Reference		Reference
	2011-2018	0.825 (0.774-0.880)	< 0.001	1.008 (0.894-1.137)	0.893	0.833 (0.780-0.889)	< 0.001	1.024 (0.905-1.159)	0.704
Sex	Female	Reference				Reference
	Male	0.997 (0.936-1.063)	0.932			0.986 (0.924-1.052)	0.67
Race	White	Reference				Reference
	Black	1.101 (0.988-1.227)	0.082			1.073 (0.959-1.201)	0.219
	Other	1.005 (0.907-1.114)	0.919			1.006 (0.905-1.117)	0.916
Marital status	Married	Reference		Reference		Reference		Reference
	Unmarried	1.217 (1.141-1.299)	< 0.001	1.061 (0.993-1.133)	0.08	1.226 (1.147-1.310)	< 0.001	1.065 (0.995-1.139)	0.068
Primary site	Head	Reference		Reference		Reference		Reference
	Body/tail	1.092 (1.006-1.185)	0.034	1.008 (0.927-1.096)	0.849	1.101 (1.013-1.197)	0.024	1.012 (0.929-1.103)	0.78
	Other	1.216 (1.106-1.336)	< 0.001	1.015 (0.922-1.118)	0.756	1.233 (1.120-1.358)	< 0.001	1.024 (0.929-1.130)	0.632
Histology grade	Grade I-II	Reference		Reference		Reference		Reference
	Grade III-IV	1.344 (1.219-1.482)	< 0.001	1.367 (1.240-1.508)	< 0.001	1.332 (1.204-1.473)	< 0.001	1.355 (1.224-1.500)	< 0.001
	Unknow	1.965 (1.818-2.125)	< 0.001	1.100 (1.005-1.204)	0.039	2.006 (1.851-2.173)	< 0.001	1.096 (0.999-1.203)	0.052
Node status	Negative	Reference		Reference		Reference		Reference
	Positive	0.835 (0.783-0.891)	< 0.001	1.209 (1.125-1.300)	< 0.001	0.837 (0.783-0.894)	< 0.001	1.227 (1.140-1.321)	< 0.001
Tumor size (cm)	< 2	Reference		Reference		Reference
	2-4	1.482 (1.317-1.668)	< 0.001	1.400 (1.242-1.578)	< 0.001	1.497 (1.325-1.692)	< 0.001	1.403 (1.239-1.587)	< 0.001
	> 4	1.854 (1.639-2.098)	< 0.001	1.505 (1.322-1.712)	< 0.001	1.875 (1.651-2.130)	< 0.001	1.492 (1.306-1.705)	< 0.001
SEER stage	Localized	Reference		Reference		Reference		Reference
	Regional	0.948 (0.860-1.045)	0.28	1.124 (1.009-1.252)	0.033	0.967 (0.874-1.070)	0.512	1.147 (1.026-1.282)	0.016
	Distant	2.058 (1.836-2.308)	< 0.001	1.723 (1.522-1.951)	< 0.001	2.154 (1.914-2.423)	< 0.001	1.782 (1.568-2.025)	< 0.001
Surgery	No	Reference		Reference		Reference		Reference
	Yes	0.337 (0.314-0.363)	< 0.001	0.352 (0.320-0.387)	< 0.001	0.322 (0.299-0.347)	< 0.001	0.334 (0.303-0.368)	< 0.001
Radiation	No	Reference		Reference		Reference		Reference
	Yes	0.850 (0.798-0.906)	< 0.001	0.818 (0.768-0.872)	< 0.001	0.851 (0.797-0.908)	< 0.001	0.816 (0.765-0.871)	< 0.001
Chemotherapy	No	Reference		Reference		Reference		Reference
	Yes	0.469 (0.428-0.513)	< 0.001	0.534 (0.485-0.589)	< 0.001	0.467 (0.425-0.512)	< 0.001	0.530 (0.480-0.586)	< 0.001

SEER: Surveillance, Epidemiology, and End Results; HR: Hazard ratio; CI: Confidence interval.

Table 4 Summary of studies on radiation therapy for elderly patients with pancreatic ductal adenocarcinoma

Ref.	No. of patients	Median age (range), years	Clinical stage	Median dose (range), Gy	Median follow-up (months)	Technique	Treatment modality	OS1	Toxicities (%)
Davila et al[14], 2009	553	> 65	I-III	NR	NR	NR	Surg: 51%	NR	NR
							Surg + CRT: 31%
							Surg + CT: 9.0%
							Surg + RT: 9.0%
Miyamoto et al[17], 2010	42	78 (75–90)	I-III	48.1 (38.9–57.3)	11.7 (2.9–41.7)	3D-CRT/IMRT	CRT: 57.1%	mOS: 8.6 mo2	Acute (G ≥ 3): 49.0
							Surg + CRT: 40.5%	mOS: 20.6 mo3	Late (G ≥ 2): NR
							CRT + Surg: 2.4%
Horowitz et al[16], 2011	49	79 (75–90)	I-II	50.0	19 (2.6–57.4)	NR	Surg + CRT: 29.5%	mOS: 22.6 mo	NR
							Surg: 70.5%	5 yr-OS: 49.7%
Kim et al[19], 2013	26	86 (80–91)	I-IV	24 (22–36)	11.6 (3.5–24.6)	SBRT	RT ± CT: 100%	LC: 11.5 mo	Acute (G ≥ 3): 0.0
								MFS: 8.4 mo	Late (G ≥ 2): 0.0
								mOS: 7.6 mo
								2 yr-OS: 6.6%
Herman et al[20], 2015	33	> 65	NR	33	13.9 (3.9–45.2)	SBRT	CT+ RT + CT ± Surg: 89.8%	mOS: 11.0 mo	NR
							RT + CT ± Surg: 10.2%	2 yr-OS: 20%
Hayman et al[15], 2015	53	77 (> 70)	NR	50 (43.2–63.0)	36	NR	Surg: 30.4%	mOS: 21.1 mo	NR
							Surg + CT: 22.3%
							Surg + CRT: 47.3%
Yechieli et al[21], 2017	20	83.2 (77-90)	I-II	35 (30–36)	5.3 (2.3–26.2)	SBRT	RT: 100%	mOS: 6.4 mo	Acute (G ≥ 3): 0.0
								2 yr-OS: 7.7%	Late (G ≥ 2): 15.0
Zhu et al[22], 2017	417	73 (65–90)	II-IV	NR (30–46.8)	11 (4–28)	SBRT	CT + RT: 11.2%	LC: 10.0 mo	Acute (G ≥ 3): 0.5
							Surg + RT: 7.7%	PFS: 8.0 mo	Late (G ≥ 3): 0.0
							RT: 81.1%	MFS: 9.5 mo
								mOS: 10.0 mo
								1 yr-OS: 35.5%
Frakes et al[18], 2017	555	75 (70–88)	I-III	NR	NR	NR	Surg + RT: 100%	mOS: 19.0 mo	NR
Sutera et al[23], 2018	145	79 (70.1-90.3)	I-III	36 Gy/3f or 24 Gy/f	12.3 (6.0–23.3)	SBRT	Surg + RT: 30.3%	mOS: 40.0 mo
							CT + RT: 53.8%	1 yr-LC: 72%	Acute (G ≥ 3): 0.7
								2 yr-LC: 63%	Acute (G ≥ 2): 4.1
							RT: 15.9%	1 yr-MFS: 62%	Late (G ≥ 3): 1
								2 yr-MFS: 47%	Late (G ≥ 2): 2

¹Reported results refers only to patients treated with radiotherapy.

²Definitive chemoradiation.

³Adjuvant chemoradiation.

CRT: Chemoradiotherapy; CT: Chemotherapy; 3D-CRT: Three-dimensional conformal radiotherapy; IMRT: Intensity modulated radiotherapy; LC: Local control; MFS: Metastasis free survival; NR: Not reported; OS: Overall survival; RT: Radiation therapy; SBRT: Stereotactic body radiotherapy; Surg: Surgery; G: Grade.