Radiation therapy for extrahepatic bile duct cancer: Current evidences and future perspectives

Table 1 Contemporary series of adjuvant radiotherapy for resected extrahepatic bile duct cancer

Ref.	Study period	Study design	No. of pts	RT dose (median)	Concurrent chemo-therapy	Subgroup	5-yr overall survival
Kim et al[16]	1995-2002	Retrospective	86	40 Gy	5-FU (96.5%)	R0 (n = 58)	46.3%	P = 0.6641
						R1 (n = 28)	41.4%
Park et al[17]	1998-2007	Retrospective	101	50 Gy	5-FU (84%)	R0 (n = 52)	44%	P = 0.2779
						R1 (n = 37)	33%
Borghero et al[35]	1984-2005	Retrospective	65	55 Gy	5-FU (52.4%), Cap (47.6%)	RT1 (n = 42)	36%	P = 0.6
				-		No RT (n = 23)	42%
Gwak et al[31]	1997-2005	Retrospective	78	50.4 Gy	FP or FL (51.6%)	RT (n = 31)	21.0%	P > 0.5
				-	-	No RT2 (n = 47)	11.6%
Kim et al[30]3	2001-2009	Retrospective	168	45 Gy	FL (99.1%)	RT (n = 115)	36.5%	P = 0.049
				-	-	No RT (n = 53)	28.2%
Ben-Josef et al[21]4	2008-2012	Phase 2	79	54-59.4 Gy	4 cycles of GemCap followed by concurrent Cap	R0 (n = 54)	67%5	P = NS
						R1 (n = 25)	60%5

¹Received adjuvant chemotherapy before chemoradiotherapy in 17% of patients;

²Received adjuvant chemotherapy in 17% of patients;

³Includes ampullary cancer as well (18.4%);

⁴Includes gallbladder cancer as well (31.6%);

⁵2-yr overall survial rate. RT: Radiotherapy; 5-FU: 5-fluorouracil; Cap: Capecitabine; FL: 5-FU plus leucovorin; GemCap: Gemcitabine plus capecitabine; NS: Not significant.

Table 2 Contemporary series of definitive radiotherapy for unresectable extrahepatic bile duct cancer

Ref.	Study period	Study design	No. of pts	EBRT (median)	Brachytherapy	Chemotherapy	Median OS (mo)
Deodata et al[44]	1991-1997	Retrospective	22	50.4 Gy	30-50 Gy (n = 12)	5-FU (95.5%)	23.01
Brunner et al[45]	1994-2001	Retrospective	25	45 Gy	10 Gy (n = 4)	FM (40%), GP (56%)	11.82
Schleicher et al[46]	1991-1999	Retrospective	30	30 Gy	24-40 Gy (n = 18)	5-FU (80%)	5.72
Takamura et al[48]	1988-1998	Retrospective	93	50 Gy	39.2 Gy3	-	122
Shin et al[49]	1986-1995	Retrospective	31	50.4 Gy	15 Gy (n = 14)	-	21%4	P = 0.015
					- (n = 17)		0%4
Yoshioka et al[50]	2000-2011	Retrospective	209	50 Gy	8-30 Gy (n = 56)	Various (57%)	31%4	P = 0.862
					- (n = 153)		40%4
Torgeson et al[42]	2004-2014	NCBD	1070	54-89 Gy	-	Various (100%)	14.5	P < 0.001
			1871	-	-		12.6
Autorino et al[47]	2002-2009	Phase 2	27	50 Gy	15-20 Gy (n = 6)	Gemcitabine (100%)	14

¹From the date of cancer diagnosis;

²From the time of radiotherapy initiation;

³mean;

⁴2-yr overall survival rate. ERRT: External beam radiotherapy; OS: Overall survival; 5-FU: 5-fluorouracil; FM: 5-FU plus mitomycin-C; GP: Gemcitabine plus cisplatin; NCDB: National Cancer Database.

Table 3 Stereotactic body radiotherapy for hilar cholangiocarcinoma

Ref.	Study period	Study design	No. of pts	RT dose	RT modality	Late toxicity ≥ Gr 3	Median OS (mo)
Kopek et al[51]1	1999-2006	Retrospective	27	45 Gy/3fx	linear accelerator	22.2% (duodenal ulcer)	10.62
Momm et al[52]	1998-2008	Retrospective	13	32-56 Gy/8-16fx	linear accelerator	None	33.53
Polistina et al[53]	2004-2009	Retrospective	10	30 Gy/3fx	Cyber Knife	None	35.53

¹Includes intrahepatic cholangiocarcinoma as well (3.7%);

²from the date of radiotherapy initiation;

³From the date of cancer diagnosis.

Table 4 Palliative radiotherapy for stent patency in hilar cholangiocarcinoma

Ref.	Study period	Study design	No. of pts	EBRT	Brachytherapy	Median OS (mo)		Median stent patency (mo)
Lee et al[60]1	2005-2008	Retrospective	18	≥ 50 Gy	-	14.0	P = 0.11	4.7	P = 0.94
			32	-	-	9.0		4.5
Isayama et al[59]	1986-2008	Retrospective	28	Median 50 Gy	24 Gy (n = 11)	22.1	P = 0.0031	50%2	P = 0.0165
			11	-	-	5.7		0%2
Shinchi et al[61]	1992-1998	Retrospective	30	Median 46 Gy3	-	10.63	P < 0.05	9.83	P = 0.0002
			10	-	-	6.43		3.73
Tan et al[62]	2007-2013	Retrospective	25	37.0-40.7 Gy	-	12.2	P = 0.025	10.9	P = 0.022
			13	-	-	8.9		6.5

¹Location not specified;

²Crude stent patency rate at 1-yr;

³mean. ERRT: External beam radiotherapy; OS: Overall survival.