Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Table 1 Rationale for the use of neoadjuvant therapy in intrahepatic cholangiocarcinoma

	Rationale for the use of neoadjuvant therapy in ICC
1	Downstaging of locally advanced tumors
2	Improve margin-negative resection rate
3	Increase receipt of systemic therapy given challenges in delivering postoperative chemotherapy
4	Prioritize the early systemic treatment of potential micrometastatic disease
5	Enhance patient selection for major surgery
6	Facilitate an in vivo test of chemotherapy’s effectiveness

ICC: Intrahepatic cholangiocarcinoma.

Table 2 Select studies on neoadjuvant systemic chemotherapy for intrahepatic cholangiocarcinoma

Ref.	Study type	Intervention	Sample size	Conversion to resection	Tumor response
Kato et al[46], 2013	Retrospective	Gemcitabine	22	8 (37%)	3 PR, 11 SD, 8 PD
Kato et al[47], 2015	Retrospective	Gemcitabine plus cisplatin	39	10 (26%)	9PR, 21 SD, 9 PD
Rayar et al[71], 2017	Retrospective	Gemcitabine and/or platinums; Y-90 TARE	45	10 (22%)	NR
Konstantinidis et al[79], 2017	Retrospective	Bevacizumab + FUDR HAI	104	8 (8%)	NR
Omichi et al[110], 2017	Retrospective	Gemcitabine based therapy	43	43 (100%)	NR
Le Roy et al[48], 2018	Retrospective	Gemcitabine plus oxaliplatin	74	39 (53%)	18 PR, 33 SD, 23 PD
Sumiyoshi et al[112], 2018	Retrospective	S-1 + IMRT	7	5 (71%)	4 PR, 1 SD, 2 PD

NR: Not reported; PR: Partial response; SD: Stable disease; PD: Disease progression; ICC: Intrahepatic cholangiocarcinoma; TARE: Transarterial radioembolization; IMRT: Intensity-modulated radiation therapy.

Table 3 Select studies on neoadjuvant transarterial chemoembolization for intrahepatic cholangiocarcinoma

Ref.	Study type	Intervention	Sample size	Conversion to resection	Tumor response
Burger et al[58], 2005	Retrospective	Cisplatin, doxorubicin, and mitomycin-C	17	2 (12%)	NR
Herber et al[59],2007	Retrospective	Mitomycin-C	15	BR	1 PR, 9 SD, 4PD
Gusani et al[60], 2008	Retrospective	Gemcitabine-based	42	NR	20 SD, 15 PD
Hyder et al[61], 2013	Retrospective – multi-institutional	cTACE (64.7%), DEB-TACE (5.6%), bland embolization (6.6%), or Y-90 (23.2%)	198	NR	56 PR, 77 SD, 29 PD
Vogl et al[62], 2012	Retrospective	Mit-C (20.9%), Gem. (7%), Mit-C +Gem (47%), Gem+ Mit-C and Cisplatin (25.1%)	115	NR	10 PR, 66 SD, 39 PD
Alibertti et al[64], 2017	Retrospective	DEB-TACE and PEG-TACE	127	4 (4%)	19 PR, 101 SD, 7 PD
Schiffman et al[65], 2011	Retrospective	EBIRI or DEB-DOX therapy	24	3 (13%)	1CR, 1PR, 13 SD, 3 PD
Kuhlmann et al[66], 2012	Prospective	Irinotecan (iDEB-TACE), mitomycin-C (cTACE)	41	1 (4%)	2 PR, 12 SD, 19 PD
Poggi et al[67], 2009	Retrospective	DEB-TACE	9	3 (33%)	4 PR, 5 SD

NR: Not reported; PR: Partial response; SD: Stable disease; PD: Disease progression; ICC: Intrahepatic cholangiocarcinoma; DEB: Drug-eluting bead

Table 4 Select studies on neoadjuvant transarterial radioembolization/selective internal radiation therapy for intrahepatic cholangiocarcinoma

Ref.	Study type	Intervention	Sample size	Conversion to resection	Tumor response
Ibrahim et al[68], 2008	Prospective	Y-90	24	1 (4%)	6PR, 15 SD, 1PD
Mouli et al[69], 2013	Retrospective	Y-90	46	5 (11%)	11 PR, 33 SD, 1 PD
Rayar et al[71], 2015	Retrospective	Gemcitabine followed by Y-90	10	8 (80%)	NR
Saxena et al[72], 2010	Retrospective	Y-90	25	1 (4%)	6 PR, 11 SD, 5 PD
Rafi et al[73], 2012	Prospective	Y-90	19	NR	2 PR, 13 SD, 4 PD
Hoffman et al[74], 2012	Prospective	Y-90	33	NR	12 PR, 17 SD, 5 PD
Riby et al[75], 2020	Retrospective	Y-90	19	19 (100%)	NR
Edeline et al[76], 2019	Phase II Trial	GemCis + Y-90	26	9 (22%)	NR

NR: Not reported; PR: Partial response; SD: Stable disease; PD: Disease progression; ICC: Intrahepatic cholangiocarcinoma.

Table 5 Select studies on neoadjuvant hepatic artery infusion for intrahepatic cholangiocarcinoma

Ref.	Study type	Intervention	Sample size	Conversion to resection	Tumor response
Jarnagin et al[77], 2009	Phase II trial	HAI	26	1 (4%)	14 PR, 11 SD, 1PD
Kemeny et al[78], 2011	Phase II trail	HAI + bevacizumab	18	3 (17%)	7 PR, 11 SD
Konstantinidis et al[79], 2015	Retrospective	HAI + chemotherapy	93	8 (4%)	NR
Massani et al[80], 2015	Retrospective	HAI	11	3 (27%)	5 PR, 2 SD,
Tanaka et al[113], 2002	Retrospective	HAI	11	1 (9%)	7 PR, 2 SD, 2 PD
Shitara et al[114], 2008	Retrospective	HAI	20	NR	1CR, 9PR, 8 SD, 2PD
Ghiringhelli et al[115], 2013	Retrospective	HAI	12	2 (17%)	8 PR, 3 SD, 1 PD

NR: Not reported; PR: Partial response; SD: Stable disease; PD: Disease progression; ICC: Intrahepatic cholangiocarcinoma; TACE: Transarterial chemoembolization.