Short-term effectiveness of radiochemoembolization for selected hepatic metastases with a combination protocol

Table 1 Assessment of target lesion response

mRECIST		RECIST		Subjective percentage of necrosis
CR	Disappearance of any intratumoral enhancement in all target lesions	CR	Disappearance of all target lesions	CR	Disappearance of any intratumoral enhancement in all target lesions
PR	At least a 30% decrease in the sum of diameters of viable target lesions	PR	At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions	PR	At least a 30% increase in the sum of target lesion necrosis percentages
SD	Any cases that do not qualify for either partial response or progressive disease	SD	Any cases that do not qualify for either partial response or progressive disease	SD	Any cases that do not qualify for either partial response or progressive disease
PD	An increase of at least 20% in the sum of the diameters of viable target lesions or new lesion appearance	PD	An increase of at least 20% in the sum of the diameters of target lesions or new lesion appearance	PD	A decrease of at least 20% in the sum of target lesion necrosis percentages or new lesion appearance

mRECIST: Modified response evaluation criteria in solid tumors; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 2 Description of lesions for each patient and local tumor control outcomes with regard to different criteria

No.	Sex	Age (yr)	No. of lesions	Location	Primary source	New lesion	mRECIST	RECIST	Necrosis	Sum of viable diameters (mm)		Sum of necrosis percentages (%)		Sum of diameters (mm)
										Baseline	Post-procedural	Baseline	Post-procedural	Baseline	Post-procedural
1	F	41	Multi	U	BRE	No	PR	SD	PR	57	18	0	100	57	44
2	F	29	Multi	U	BRE	No	SD	SD	SD	34	34	5	5	34	34
3	F	35	1	U	BRE	No	PR	SD	PR	50	33	30	50	60	45
4	F	39	Multi	B	BRE	No	PR	SD	PR	57	39	20	100	65	54
5	F	38	Multi	B	BRE	Yes	PD	PR	PD	72	-1	30	-	72	-
6	F	27	2	U	CAR	No	CR	PR	CR	92	0	0	200	92	42
7	M	81	3	U	CRC	No	PR	SD	PR	73	23	40	95	107	95
8	M	40	1	U	CRC	No	PR	PR	SD	55	33	5	5	55	33
9	F	41	1	U	CRC	No	PR	SD	PR	65	45	40	80	80	68
10	F	47	1	U	CRC	No	PR	SD	PR	144	103	50	80	226	217
11	F	59	1	U	CRC	Yes	PD	PD	PD	70	-	0	-	70	-
12	M	60	Multi	U	CRC	Yes	PD	PD	PD	50	-	0	-	50	-
13	M	57	1	U	CRC	Yes	PD	PD	PD	25	-	70	-	35	-
14	M	55	1	U	CRC	No	PD	PD	SD	56	102	5	5	56	102
15	M	77	Multi	U	CRC	No	SD	SD	SD	107	107	15	15	116	116
16	F	62	Multi	B	CRC	No	PR	SD	SD	40	7	155	195	68	55
17	F	57	Multi	B	CRC	No	PR	SD	PR	50	35	90	180	65	55
18	M	74	Multi	B	CRC	No	PR	SD	PR	213	116	10	130	213	159
19	F	48	Multi	B	CRC	No	PR	SD	PR	245	160	5	120	265	260
20	F	51	Multi	U	LUN	No	PR	SD	PR	142	61	20	175	150	127

¹For patients with new lesions in the follow-up scan, the measurements were not performed and the patient was marked as progressive disease (PD); CR: Complete response; PR: Partial response; SD: Stable disease; U: Unilobar; B: Bilobar; F: Female; M: Male; BRE: Breast cancer; CRC: Colorectal carcinoma; CAR: Carcinoid tumor; LUN: Lung cancer; mRECIST: Modified response evaluation criteria in solid tumors.

Table 3 Studies on Yttrium-90 radioembolization for metastatic hepatic lesions from mixed sources

Study	Procedure	Agent	Absorbed dose or mean activity delivered1	Number of patients	Response criteria	Response measured at (months post treatment)	Response rate	Complications
Blanchard et al[49], 1989	Radioembolization	90Y plastic microspheres	NA	15	WHO	NA	Partial response in 5 (33.3%), minimal response in 2 (13.3%)	Gastritis or gastric ulceration in 6 (in three this was proven to be due to unintended infusion of microspheres into the gastric circulation)
Andrews et al[50], 1994	Radioembolization	90Y glass microspheres	150 Gy	24	WHO	2	Partial response in 5 (20.8%), minimal response in 4 (16.7%), stable disease in 7 (29.2%), progressive disease in 8 (33.3%)	Mild gastrointestinal symptoms in 4 (unrelated to treatment)
Miller et al[7], 2007	Radioembolization	90Y glass microspheres	100-120 Gy	42	WHO	2.32	Complete/partial response in 8 (19%), stable disease in 22 (52%), progressive disease in 23	Radiation cholecystitis in 10, liver edema in 18
					RECIST	3.92	Complete/partial response in 10 (24%), stable disease in 21 (50%), progressive disease in 23
					Necrosis	12	Complete/partial response in 19 (45%)
					Combined	1.12	Complete/partial response in 21 (50%), stable disease in 11 (26%)
Sato et al[8], 2008	Radioembolization	90Y glass microspheres	112.8 Gy/1.83 GBq	137	WHO	1-3	Complete response (2.1%), partial response (40.7%)	Fatigue (56%), vague abdominal pain (26%), nausea (23%)
Lim et al[51], 2005	Radioembolization	90Y resin microspheres	NA	46	RECIST	2	Partial response in 12 (27%), stable disease in 12 (27%), progressive disease in 19 (44%)	Between 2 and 8 wk of lethargy, anorexia, nausea and right upper quadrant pain in most patients, severe gastric/duodenal ulceration in 4 (8%), portal hypertension in 1, radiation hepatitis in 1
Yu et al[52], 2006	Radioembolization	90Y resin microspheres	42 Gy	49	RECIST	NA	Response rate of 29%	Fatigue in 18 (37%), vague abdominal pain in 10 (20%), nausea/vomiting in 10 (20%), ascites and/or leg edema in 3 (6%)
Szyszko et al[53], 2007	Radioembolization	90Y resin microspheres	1.9 GBq	21	RECIST	1-2	Partial response in 2 (13%), stable disease in 9 (60%), progressive disease in 4 (27%)	NA
Stuart et al[54], 2008	Radioembolization	90Y resin microspheres	NA	30	RECIST	NA	Partial response or stable disease in 14 (47%)	Gastrointestinal ulceration in 1 (3%)
Kennedy et al[55], 2009	Radioembolization	90Y resin microspheres	1.1 ± 0.6 GBq	5023	RECIST	3	Complete response in 23 (4.5%), partial response in 48 (9.5%), stable disease in 386 (76.8%), progressive disease in 45 (9%)	Fatigue and upper abdominal pain (29%), gastritis and overt gastric ulceration (2%), severe liver disease (4%)
Peynircioğlu et al[43], 2010	Radioembolization	90Y resin microspheres	1.24 GBq	10	RECIST	1-2	All patients had at least partial response of the target lesions	Post-procedural mild to moderate fatigue in all patients for 7 d, with mild to moderate fever and abdominal pain in some patients
Omed et al[56], 2010	Radioembolization	90Y resin microspheres	NA	11	RECIST	NA	Partial response (20%), stable disease (50%), progressive disease (30%)	No major complications, 82% of patients experienced side-effects, mainly nausea, vomiting and abdominal pain
Cianni et al[57], 2010	Radioembolization	90Y resin microspheres	1.64 Gbq	110	RECIST	2	Complete/partial response in 45, stable disease in 42, progressive disease in 23	Hepatic failure in 1, gastritis in 6, cholecystitis in 2

¹The absorbed dose in Gy and/or the mean delivered activity in Gbq are provided with respect to their availability;

²median;

³the total number of patients in the study was 680, but the response evaluation criteria in solid tumor (RECIST) criteria were only available for 502 patients. ⁹²Y: Yttrium-90; WHO: World Health Organization; NA: Not available.

Table 4 Studies on chemoembolization for metastatic hepatic lesions with cisplatin, doxorubicin and mitomycin

Study	Primary diagnosis	Procedure	Chemotherapeutic agents	Embolic material	Number of patients	Response criteria	Response measured at months treatment	Response rate	Complications
Diaco et al[58], 1995	Carcinoid tumor	Chemoembolization	Cisplatin, doxorubicin, mitomycin	NA	10	WHO	NA	Partial response (60%), stable disease (30%)	NA
Drougas et al[59], 1998	Carcinoid tumor	Chemoembolization	Doxorubicin (60 mg), cisplatin (100 mg), and mitomycin (30 mg)	Polyvinyl alcohol	131	WHO	3	Partial response in 1 (8%), minimal response in 10 (77%), stable disease in 1 (8%), progressive disease in 1 (8%)	Nausea/vomiting in 100%, increased transaminases in 100%, pain in 100%, fever in 29%, myelosuppression in 29%, arterial thrombosis in 8%, dysrhythmia in 8%, mental status changes in 4%
Tellez et al[60], 1998	Colorectal carcinoma	Chemoembolization	Cisplatin, doxorubicin, mitomycin	Angiostat (a bovine collagen material)	27	Designed by authors2	NA	Radiological response in 17 of 27 patients (63%)	Fever in 83%, RUQ pain in 100%, nausea/vomiting in 83%, gastritis in 17%, lethargy in 60%
Buijs et al[45], 2007	Breast cancer	Chemoembolization	Doxorubicin (50 mg), cisplatin (100 mg), and mitomycin (10 mg) in a 1:1 mixture with iodized oil	300- to 500-μm embolic microspheres	143	RECIST	1-2	No complete response, partial response in 7 lesions (26%)6	NA
Ruutiainen et al[61], 2007	Neuroendocrine tumor	Chemoembolization	Cisplatin, doxorubicin, mitomycin in a mixture with iodized oil	150- to 250-μm granular polyvinyl alcohol particles	44	RECIST	1	88% partial response/stable disease	High incidence of postembolization syndrome, severe pain in 3 sessions, severe nausea in 1 session, severe vomiting in 1 session, severe GGT/ALP elevation in 4 sessions, severe AST elevation in 1 session, severe ALT elevation in 1 session, severe infection in 1 session
Artinyan et al[44], 2008	Mixed	Chemoembolization	Doxorubicin (50 mg), mitomycin (10 mg), and cisplatin (150 mg)	Polyvinyl alcohol microspheres (300-700 μm)	614	RECIST	At least 1	Partial response in 9 (14.8%), progressive disease in 3 (4.9%)	Bleeding in 2 patients (2%), renal failure in 6 patients (5%), hepatic failure in 7 patients (6%), infection in 3 patients (3%), mortality in 30 d in 7 patients (6%)
Buijs et al[48], 2008	Ocular melanoma	Chemoembolization	Doxorubicin (50 mg), cisplatin (100 mg), and mitomycin (10 mg) in a 1:1 mixture with iodized oil	300- to 500-μm embolic microspheres	65	RECIST	1-2	No complete response, partial response in 8 lesions6	NA
Albert et al[62], 2011	Colorectal carcinoma	Chemoembolization	Cisplatin, doxorubicin, mitomycin in a mixture with ethiodized oil	Polyvinyl alcohol	956	RECIST	NA	Partial response in 9 (14.8%), stable disease in 49 (80.3%), progressive disease in 3 (4.9%)	NA

¹There were 15 patients at first, however one died before the follow up imaging and one patient’s follow-up was out of state. Three patients only received hepatic artery embolization;

²at least 75% decrease in the density of lesions consistent with necrosis or 25% decrease in the size of the lesions without the development of concomitant lesions;

³twenty-seven lesions;

⁴the total number of patients was 119, but for 61 patients the response evaluation criteria in solid tumors (RECIST) criteria were available;

⁵twenty-one lesions, reporting by patient, all patients were considered non-responders to transcatheter arterial chemoembolization because the total tumor burden did not decrease by 30% in any given patient;

⁶ninety-five of 141 treatment cycles were evaluable for response. The response rate is calculated per treatment cycle. NA: Not available; RUQ: Right upper quadrant; WHO: World Health Organization; GGT/ALP: Gamma-glutamyl transpeptidase/alkaline phosphatase; AST/ALT: Aspartate aminotransferase/alanine aminotransferase.