Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma: Review of the literature

Table 1 Papers about neoadjuvant therapy before resection considered in this review

Author	Yr	Type of study	Patients treated with NA RCT	Resectability	Neoadjuvant regimen	% of R0 (R0/resected)	Results achieved	Conclusions
McMasters at al[11]	1997	Non randomized, prospective	5 hCCA and 4 dCCA	All unresectable	5-FU at 300 mg/m2, EBRT to 50.4 or 45 Gy	100% (9/9)	Recurrence for hCCA: 0%	NA RCT can safely allow R0 resection.
Nelson et al[14]	2009	Retrospective	12 (hCCA and dCCA)	10 unresectable	5-FU, EBRT to 50.4 Gy (11/12) ± brachitherapy (5/12)	91% (11/12)	Better trend in 5-yr survival rate for NA RCT group	NA RCT can safely allow R0 resection.
Jung et al[15]	2015	Retrospective	12, all hCCA	All unresectable	5-FU/Gemcitabine, EBRT to 50.4 or 45 Gy	83,3% (10/12)	Better R0 rate for NA RCT group; no advantage in DFS and OS	NA RCT can safely allow R0 resection, without improving DFS and OS.
Sumiyoshi et al[16]	2018	Retrospective	8 hCCA	All unresectable	S-1, EBRT to 50 Gy	71,4% (5/7)	Better DFS and OS for patients who underwent surgery after downstaging with NA RCT	NA RCT can safely allow R0 resection, improved DFS and OS for patients operated.
Katayose et al[18]	2015	Non randomized, prospective	24 (hCCA and dCCA)	All advanced, possibly resectable	Gemcitabine 600 mg/m2, EBRT to 45 Gy	80,9 % (17/21)	R0 rate: 80.9% of patients operated, 70.8% of all patients enrolled	NA RCT followed by surgery effective and well tolerated, DFS and OS yet to determine.
Tada et al[19]	2012	Case report	1 hCCA	Unresectable	Gemcitabine + S-1	1/1	R0 resection with portal resection, no recurrence at 29 mo	NA CT can allow R0 resection.
Sano et al[20]	2011	Case report	1 hCCA	Unresectable	Gemcitabine	1/1	R0 resection with portal and arterial resection, no recurrence at 18 mo	NA CT can allow R0 resection.

NA RCT: Neoadjuvant radiochemotherapy; hCCA: Hilar cholangiocarcinoma; dCCA: Distal cholangiocarcinoma; EBRT: External beam radiation therapy; 5-FU: 5-Fluorouracil; DFS: Disease free survival; OS: Overall survival.