Efficacy of Radioembolization with 166Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study

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FIGURE 1.
Flowchart of study. *Metastases could not be adequately targeted, extrahepatic tissue was also targeted, or there were more than 3 injection positions. ^†Laboratory experiments indicated need to optimize microsphere production process; treatments were halted until optimization was complete.
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FIGURE 2.
Kaplan–Meier estimate of median overall survival was 14.1 mo (95% CI, 8.2 mo–∞) for patients with colorectal disease and disease control of target lesions at 3 mo, and 7.1 mo (95% CI, 3.3 mo–∞) for patients with progressive target lesions at 3 mo (P = 0.44). Data of 1 patient are missing (Fig. 1).
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FIGURE 3.
(A) Median quality-of-life (QoL) scores per time point (higher score = better QoL). (B) Median symptom scores per time point (higher score = worse symptoms).

TABLE 1

Baseline Characteristics of Treated Patients (n = 38)

Characteristic	Value
Age (y)	66 (41–84)
Sex
Male	22 (58%)
Female	16 (42%)
World Health Organization performance status
0	32 (84%)
1	5 (13%)
2	1 (3%)
Primary malignancy
Colorectal	23 (61%)
Breast	4 (11%)
Cholangiocarcinoma	4 (11%)
Neuroendocrine tumor	2 (5%)
Uveal melanoma	2 (5%)
Pancreatic cancer, gastric cancer, or thymoma	3 (8%)
Time since diagnosis (mo)	28 (4–95)
Occurrence of liver metastases
Synchronous	19 (50%)
Metachronous	19 (50%)
Time since liver metastases (mo)	18 (3–92)
Extrahepatic disease on ¹⁸F-FDG PET/CT
Lung	8/10 (80%)
Lymph node	4/10 (40%)
Skeletal	2/10 (20%)
Liver mass (kg)	2.0 (1.2–4.0)
Tumor load on contrast-enhanced CT
0%–25%	30 (79%)
25%–50%	6 (16%)
>50%	2 (5%)

Qualitative data are expressed as numbers followed by percentages in parentheses; continuous data are expressed as median followed by range in parentheses.

TABLE 2

Treatment Characteristics of Colorectal Cancer Patients (n = 23)

Characteristic	Value
Chemotherapy (prior to study inclusion)
Total	23 (100%)
Capecitabine	22 (96%)
Oxaliplatin	21 (91%)
Bevacizumab	14 (61%)
Irinotecan	11 (48%)
5-fluorouracil	6 (26%)
Leucovorin	5 (22%)
Panitumumab	4 (17%)
Cetuximab	1 (4%)
Dabrafenib	1 (4%)
Tegafur-uracil	1 (4%)
Targeted part of liver
Whole liver	36 (95%)
Right lobe	2 (5%)
Left lobe	0 (0%)
Treatment sessions
1	36 (95%)
2	2 (5%)
Specific activity (MBq/mg)^*	11.26 (4.95–21.34)
Infused activity (MBq)^*	6,412 (2,213–13,189)
Administration of treatment dose^†	96% (41%–99%)
Adequate administration of activity (>90%)^‡	26/37 (70%)
Absorbed liver dose (Gy)	51 (26–69)
Predicted lung shunt (^99mTc-MAA)	3.2% (0.01%–19.3%)
Actual lung shunt (¹⁶⁶Ho)	0.02% (0%–0.7%)

↵* All injections combined (including scout dose), at respective time of injection.
↵† Percentage of prepared.
↵‡ In other patients, stasis occurred or infusion was stopped because of pain.
Qualitative data are expressed as numbers followed by percentages in parentheses; continuous data are expressed as median followed by range in parentheses.

TABLE 3

Response on Contrast-Enhanced CT

↵* Not evaluable, or disease progression was inferred for patients with missing data.
Data are n followed by percentage in parentheses. Timing was at median of 90 d (range, 76–104 d) after treatment at 3 mo, 181 d (152–195) at 6 mo, 278 d (252–312) at 9 mo, and 369 d (368–369) at 12 mo.

TABLE 4

Adverse Events—Clinical

Adverse event	Any time	≤1 wk	>1 wk	Grade 3 or 4
Nausea	74% (28)	71% (27)	34% (13)	8% (3)
Abdominal pain	71% (27)	68% (26)	47% (18)	18% (7)
Fatigue	66% (25)	26% (10)	61% (23)	3% (1)
Vomiting	66% (25)	58% (22)	18% (7)	3% (1)
Back pain	34% (13)	24% (9)	11% (4)	0
Anorexia	26% (10)	13% (5)	21% (8)	0
Edema limbs	18% (7)	0	18% (7)	0
Fever	18% (7)	11% (4)	11% (4)	0
Constipation	16% (6)	5% (2)	11% (4)	0
Dizziness	16% (6)	11% (4)	11% (4)	0
Allergic reaction	13% (5)	13% (5)	5% (2)	0
Arthralgia	13% (5)	3% (1)	11% (4)	0
Dyspnea	13% (5)	0	13% (5)	0
Shoulder pain	13% (5)	5% (2)	11% (4)	0
Ascites	11% (4)	0	11% (4)	3% (1)
Chills	11% (4)	0	11% (4)	0
Dysgeusia	11% (4)	3% (1)	11% (4)	0
Gastric stenosis	3% (1)	0	3% (1)	3% (1)
Hepatic failure^*	3% (1)	0	3% (1)	3% (1)
Liver abscesses	3% (1)	0	3% (1)	3% (1)
Paroxysmal atrial tachycardia	3% (1)	0	3% (1)	3% (1)
Thoracic pain	3% (1)	3% (1)	3% (1)	3% (1)
Upper gastrointestinal hemorrhage	3% (1)	0	3% (1)	3% (1)

↵* We suspected mix of disease progression and radioembolization induced liver disease. This patient is also included in parameter “ascites.”
Numbers of events are in parentheses. Adverse events are those with incidence of >10% or CTCAE grade 3 or 4, after treatment, regardless of relation with ¹⁶⁶Ho radioembolization.

TABLE 5

Adverse Events—Laboratory Examinations

Adverse event	Grade 1–2	Grade 3	Grade 4	NA
γ-glutamyl transferase	6	28	4	0
Lymphocytopenia	15	6	1	0
Bilirubin	12	0	1	0
Alkaline phosphatase	32	6	0	0
Aspartate aminotransferase	35	3	0	0
Alanine aminotransferase	28	2	0	0
Lactate dehydrogenase	27	0	0	0
Hemoglobin	26	0	0	0
Ammonia	22	0	0	0
Albumin	20	0	0	0
Platelet count	19	0	0	0
Erythrocytes	15	0	0	0
Sodium	15	0	0	2
Leukocytes	14	0	0	0
Creatinine	12	0	0	0
Potassium	9	0	0	2
Total protein	9	0	0	4
Calcium (ionized)	8	0	0	3
Magnesium	6	0	0	4
Phosphorus	6	0	0	3
Urea	6	0	0	3
Chloride	5	0	0	4
Bicarbonate	4	0	0	4