Results of adjuvant radiation therapy for locoregional perihilar cholangiocarcinoma after curative intent resection

Figures & data

Figure 1 Patient selection flowchart.

Abbreviations: ICD-O-3, International Classification of Diseases for Oncology, 3rd Edition; SEER, Surveillance, Epidemiology and End Results.

Table 1 Demographics of patients with pCCA between treatment cohorts before and after propensity score matching

Variables	Before propensity score matching			After propensity score matching
	Adjuvant RT (n=762)	Surgery alone (n=1,155)	P-value	Adjuvant RT (n=651)	Surgery alone (n=651)	P-value
Age (years)			<0.001			0.585
≤49	92	94		64	55
50–59	170	173		148	130
60–69	239	369		216	236
70–79	212	375		184	190
80+	49	144		39	40
Gender			0.044			1
Men	481	676		411	411
Women	281	479		240	240
Race			0.184			1
White	595	918		537	537
Black	44	81		27	27
Others	123	156		87	87
Year of diagnosis			0.361			0.287
1988–1993	91	152		86	74
1994–1999	139	203		106	122
2000–2004	257	351		197	215
2005–2009	275	449		262	240
Tumor grade			0.639			1
Well or moderate	458	718		406	406
Poor or undifferentiated	226	321		191	191
Unknown	78	116		54	54
LN status			<0.001			1
Negative	389	724		347	347
Positive	334	372		286	286
Unknown	39	59		18	18
Tumor size (mm)			0.176			0.339
≤20	263	447		255	230
>20	255	359		204	212
Unknown	244	349		192	209
Tumor stage			<0.001			1
Localized (T1–T2)	100	255		83	83
Regional (T3–T4 and/or node positive)	655	886		567	567
Unknown	7	14		1	1
Extent of surgery			0.804			1
Radical	402	616		355	355
Limited	360	539		296	296

Abbreviations: LN, lymph node; pCCA, perihilar cholangiocarcinoma; RT, radiation therapy.

Figure 2 Kaplan–Meier analysis of (A) overall and (B) cancer-specific survival of the adjuvant RT (n=762) and surgery alone (n=1,155) groups before propensity score matching.

Abbreviation: RT, radiation therapy.

Figure 3 Kaplan–Meier analysis of (A) overall and (B) cancer-specific survival of the adjuvant RT (n=651) and surgery alone (n=651) groups after propensity score matching.

Abbreviation: RT, radiation therapy.

Table 2 Univariate analysis of the matched population for overall and cause-specific survival

Variables	Overall survival		Cause-specific survival
	Median (months)	P-value	Median (months)	P-value
Age (years)		<0.001		0.178
≤49	24		16
50–59	25		19
60–69	22		18
70–79	21		17
80+	21		18
Gender				0.258
Men	23	0.086	18
Women	19		16
Race		0.092		0.888
White	22		17
Black	18		16
Others	27		19
Year of diagnosis		0.421		0.001
1988–1993	23		19
1994–1999	23		19
2000–2004	22		18
2005–2009	22		17
Tumor grade		0.005		0.008
Well or moderate	24		19
Poor or undifferentiated	18		15
Unknown	25		18
LN status		<0.001		<0.001
Negative	31		21
Positive	17		15
Unknown	16		10
Tumor size (mm)		<0.001		0.057
≤20	26		19
>20	20		17
Unknown	21		17
Tumor stage		<0.001		<0.001
Localized (T1–T2)	37		27
Regional (T3–T4 and/or node positive)	20		17
Unknown	3
Extent of surgery		0.851		0.584
Radical	22		18
Limited	23		18
Treatment		0.978		0.554
Adjuvant RT	22		17
Surgery alone	23		18

Abbreviations: LN, lymph node; RT, radiation therapy.

Table 3 Multivariate analysis of the matched population for overall and cause-specific survival

Variables	Overall survival			Cause-specific survival
	Hazard ratio	95% CI	P-value	Hazard ratio	95% CI	P-value
Age (years)
≤49	0.586	0.428–0.803	0.001
50–59	0.655	0.500–0.859	0.002
60–69	0.796	0.617–1.028	0.080
70–79	0.913	0.706–1.182	0.491
80+	Reference
Gender
Men	0.957	0.846–1.083	0.490
Women	Reference
Race
White	1.051	0.880–1.255	0.580
Black	1.461	1.054–2.035	0.023
Others	Reference
Year of diagnosis
1988–1993				0.729	0.570–0.931	0.011
1994–1999				0.740	0.605–0.905	0.003
2000–2004				0.875	0.739–1.036	0.121
2005–2009				Reference
Tumor grade
Well or moderate	Reference			Reference
Poor or undifferentiated	1.164	1.021–1.328	0.024	1.254	1.072–1.466	0.005
Unknown	0.940	0.752–1.176	0.588	1.072	0.832–1.380	0.591
LN status
Negative	Reference			Reference
Positive	1.552	1.365–1.763	<0.001	1.422	1.223–1.654	<0.001
Unknown	1.753	1.215–2.527	0.003	3.013	1.889–4.807	<0.001
Tumor size (mm)
≤20	Reference			Reference
>20	1.229	1.063–1.422	0.005	1.089	0.915–1.296	0.337
Unknown	1.439	1.245–1.662	<0.001	1.120	0.945–1.328	0.190
Tumor stage
Localized (T1–T2)	Reference			Reference
Regional (T3–T4 and/or node positive)	1.326	1.085–1.621	0.006	1.281	1.007–1.630	0.044
Unknown	0.868	0.205–3.667	0.847
Treatment
Adjuvant RT	1.005	0.893–1.131	0.938	0.971	0.845–1.115	0.674
Surgery alone	Reference			Reference

Abbreviations: CI, confidence interval; LN, lymph node; RT, radiation therapy.

Table S1 Survival analysis in the propensity score-matched treatment cohorts for patients with high-risk tumor characteristics

Variables	Overall survival		Cancer-specific survival
	Median (months)	P-value	Median (months)	P-value
Regional tumor stages (T3–T4 and/or node positive)		0.901		0.494
Surgery alone	21		17
Adjuvant RT	20		17
Positive LN		0.689		0.851
Surgery alone	17		15
Adjuvant RT	17		16
Poor or undifferentiated grade		0.995		0.843
Surgery alone	18		15
Adjuvant RT	18		15

Abbreviations: LN, lymph node; RT, radiation therapy.

Table S2 Published survival outcomes with or without adjuvant RT for resected pCCA

Series	Year	N	OS (%)		Median survival (months)		Survival benefit from adjuvant RT
			Surgery alone	Adjuvant RT	Surgery alone	Adjuvant RT
Cameron et al^Citation1	1990	53	3 years OS: 21 5 years OS: 0	3 years OS: 21 5 years OS: 11	NS	NS	Yes
González González et al^Citation2	1990	55	3 years OS: 10	3 years OS: 31	8	19	Yes
Pitt et al^Citation3	1995	50	NS	NS	15	14	No
Todoroki et al^Citation4	2000	63	5 years OS: 13.4	5 years OS: 39.2	10	36	Yes
Gerhards et al^Citation5	2003	84	5 years OS: 11	5 years OS: 19	8	NS	Yes
Sagawa et al^Citation6	2005	69	3 years OS: 33.3	3 years OS: 40.9	NS	NS	No
Cheng et al^Citation7	2007	75	NS	NS	NS	NS	Yes

Abbreviations: N, number of patients; NS, not specified; OS, overall survival; pCCA, perihilar cholangiocarcinoma; RT, radiation therapy.

CameronJLPittHAZinnerMJKaufmanSLColemanJManagement of proximal cholangiocarcinomas by surgical resection and radiotherapyAm J Surg1990159191971688486

 PubMed Web of Science ®Google Scholar

González GonzálezDGerardJPManersAWResults of radiation therapy in carcinoma of the proximal bile duct (Klatskin tumor)Semin Liver Dis19901021311412162565

 PubMedGoogle Scholar

PittHANakeebAAbramsRAPerihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survivalAnn Surg199522167887977794082

 PubMed Web of Science ®Google Scholar

TodorokiTOharaKKawamotoTBenefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinomaInt J Radiat Oncol Biol Phys200046358158710701737

 PubMed Web of Science ®Google Scholar

GerhardsMFvan GulikTMGonzález GonzálezDRauwsEAGoumaDJResults of postoperative radiotherapy for resectable hilar cholangiocarcinomaWorld J Surg200327217317912616432

 PubMed Web of Science ®Google Scholar

SagawaNKondoSMorikawaTOkushibaSKatohHEffectiveness of radiation therapy after surgery for hilar cholangiocarcinomaSurg Today200535754855215976951

 PubMed Web of Science ®Google Scholar

ChengQLuoXZhangBJiangXYiBWuMPredictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survivalEur J Surg Oncol200733220220717088040

 PubMed Web of Science ®Google Scholar