Ann Surg Oncol (2015) 22:794–802 DOI 10.1245/s10434-014-4164-x
ORIGINAL ARTICLE – HEPATOBILIARY TUMORS
Is Yttrium-90 Radioembolization a Viable Treatment Option for Unresectable, Chemorefractory Colorectal Cancer Liver Metastases? A Large Single-Center Experience of 302 Patients Akshat Saxena, MBBS, BMedSc1,2, Baerbel Meteling, BVetMed, PhD1, Jada Kapoor, MBBS, BMedSc2, Sanjeev Golani, MBBS1, David L. Morris, MD, PhD2, and Lourens Bester, MBChB, BSc1 Department of Interventional Radiology, St Vincent’s Hospital Sydney, Darlinghurst, NSW, Australia; 2UNSW Department of Surgery, St George Hospital, Kogarah, NSW, Australia 1
ABSTRACT Introduction. We report the largest series to date on the safety and efficacy of yttrium-90 (90Y) radioembolization for the treatment of unresectable, chemorefractory colorectal cancer liver metastases (CRCLM). Methods. A total of 302 patients underwent resin-based 90Y radioembolization for unresectable, chemorefractory CRCLM between 2006 and 2013 in Sydney, Australia. All patients were followed up with imaging studies at regular intervals until death. Radiologic response was evaluated with the response criteria in solid tumors criteria. Clinical toxicities were prospectively recorded. Survival was calculated by the Kaplan–Meier method, and potential prognostic variables were identified on univariate and multivariate analysis. Results. Median follow-up in the complete cohort was 7.2 months (range 0.2–72.8), and the median survival after 90Y radioembolization was 10.5 months with a 24-month survival of 21 %. On imaging follow-up of 293 patients who were followed up beyond 2 months, complete response to treatment was observed in 2 patients (1 %), partial response in 111 (38 %), stable disease in 96 (33 %), and progressive disease in 84 (29 %). Four factors were independently associated with a poorer prognosis: extensive tumor volume, number of previous lines of chemotherapy, poor radiological response to treatment, and low preoperative hemoglobin. One hundred fifteen (38 %) developed clinical toxicity after treatment; most
Ó Society of Surgical Oncology 2014 First Received: 1 December 2013; Published Online: 17 October 2014 A. Saxena, MBBS, BMedSc e-mail:
[email protected]
complications were minor (grade I/II) and resolved without active intervention. Conclusions. 90Y radioembolization is a safe and effective treatment for unresectable, chemorefractory CRCLM.
Colorectal cancer is a leading cause of cancer-related death worldwide. In 2012, approximately 1.36 million new cases were diagnosed worldwide and 694,000 patients died from this disease.1 The liver is the most common site of metastases from CRC; up to 80 % of patients develop colorectal cancer liver metastases (CRCLM) during the course of their disease.2 Surgical extirpation of CRCLM offers the only opportunity for cure but is only feasible in a minority of patients (\25 %).3 The outcomes of patients with unresectable CRCLM are generally poor but have improved in the past two decades. Advances in chemotherapeutic and biologic agents have increased overall survival and allowed an increased number of patients to be downstaged for potentially curative surgery. Nevertheless, a significant proportion of patients have disease refractory to contemporary systemic chemotherapy treatments. The optimal management of these patients is still unclear and represents an oncological dilemma. 90Y radioembolization is a potentially effective treatment option for unresectable, chemorefractory CRCLM. It has been shown to be a safe and effective treatment for both primary and metastatic hepatic tumors, including chemorefractory CRCLM. Unfortunately, the small sample size of previous studies has precluded this treatment from being more readily adopted. As a primary objective, we evaluated the safety and survival outcomes of a large group of patients with chemorefractory CRCLM who underwent 90Y radioembolization at a single Australian institute. As a
Radioembolization of CRCLM
secondary objective, prognostic factors for overall survival and predictors of a good treatment response were identified. To our knowledge, this is the largest series to evaluate the early and late outcomes after 90Y radioembolization of CRCLM.
METHODS This retrospective study was approved by a local institutional review board. Informed consent was obtained from all patients. A total of 302 patients with unresectable, chemorefractory CRCLM were treated by selective internal radiation therapy with 90Y microspheres (SIR-spheres, Sirtex Medical, Sydney, Australia) between May 2006 and September 2012. Inclusion criteria were as follows: (a) radiologically proven CRCLM carcinoma not amenable to curative surgical resection; (b) failed at least one line of systemic chemotherapy; (c) aged 18–85 years; (d) ability to undergo angiography and selective visceral catheterization; (e) Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and (f) adequate hematology (granulocyte count C1.5 9 109/L, platelets C50 9 109/L), renal function (creatinine level B2.0 mg/dL), and hepatic function (bilirubin level B2.0 mg/dL). Patients with limited extrahepatic disease not deemed clinically important were not excluded. Before 90Y treatment, patients underwent routine baseline serology, including liver function tests and computerized tomography (CT) imaging scans of the liver. In addition, each patient underwent a liver angiography with 99 m technetium-labeled macroaggregated albumin (99mTc-MAA) scintigraph to identify any aberrant hepatic anatomy and percentage of lung shunting. Temporary balloon occlusion was performed if arteriovenous lung shunting was [20 % on 99mTc-MAA to reduce the risk of pneumonitis.4 The total volume of the liver and the volume of the right and left lobes were calculated using preoperative CT scans. Similarly, the total percentage of liver replacement by tumor and the percentage replacement in the right and left lobes were calculated using preoperative CT scans. Activity of 90Y treatment was measured in gigabecquerels (GBq) and adjusted to tumor volume and lung shunting fraction. Dosages were calculated according to patient surface area, as previously described.5 A standard dose of 90Y radioactivity contains approximately 50 million resin microspheres measuring 29–35 lm each and provides 2 GBq. 90Y is a pure b emitter with a half-life of 64.2 h and decays into stable zirconium-90. The beta emission of 90Y has a mean tissue penetration of 2.5 mm (maximum of 10 mm) and has an average energy emission of 0.937 MeV. The microspheres were injected through a temporary hepatic artery catheter placed
795
percutaneously through the femoral or brachial artery. In the majority of patients, approximately two-thirds of microspheres were injected into the right hepatic artery and one-third into the left hepatic artery. In patients who had disease primarily confined to one lobe, dose distribution was adjusted accordingly. Following treatment, all patients were hospitalized overnight as per the departmental protocol. Patients were initially followed up after 1 month and then at 3-month intervals until death. Blood, biochemical and tumor markers in addition to abdominal CT scans were obtained and assessed at each follow-up visit. Study Methods We prospectively collected and reviewed patient clinicopathologic and treatment-related data. The primary outcome of this study was overall survival and radiological hepatic tumor response. Radiological response was assessed by an experienced radiologist in accordance with the response criteria in solid tumors (RECIST) guidelines by comparison of each follow-up examination with the baseline examination.6 Secondary outcomes included treatment safety and prognostic factors for overall survival and treatment response. Statistical Analysis Clinicopathological and treatment-related variables were analyzed for an association with a good treatment response (partial response (PR) or stable disease) and overall survival. Categorical variables were compared using Chi squared analysis or Fisher’s exact test where appropriate. Survival analysis was performed by using Kaplan–Meier method and compared using the log-rank test. Patients lost to follow-up were censored at the last follow-up date. To assess the variation in each liver function test over the previous follow-up, we used the one-way analysis of variance. All statistical analyses were performed using the Statistical Package for Social Sciences for Windows (Version 17.5; SPSS GmbH, Munich, Germany). A significant difference was defined as p \ 0.05. RESULTS Patient Characteristics A total of 302 patients with CRLCM underwent treatment with 90Y microspheres between December 2005 and July 2013. A summary of patient clinicopathological and treatment-related variables is provided in Table 1. There were 195 (65 %) males. The mean age of patients at the
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A. Saxena et al.
TABLE 1 Summary of clinicopathological and treatment-related factors of 302 patients with CRCLM who underwent 90Y radioembolization Clinicopathological and treatment-related factors
All patients
Previous lines of chemotherapy 1
2
[2 52
Total
302
159
91
Sex
–
–
–
–
Male
195
106
54
35
Female
107
53
37
17
Age at time of resection (year)
–
Mean (±SD)
63.7 ± 11.0
65.4 ± 10.2
61.2 ± 12.1
62.7 ± 10.7
\64 C64
145 157
74 85
45 46
26 26
Replacement of liver by tumor (%)
–
–
–
–
0–25
163
103
41
19
26–50
97
40
34
23
51–75
26
12
9
5
–
–
–
–
Bilobar
261
141
79
41
Unilobar
41
18
12
11
–
–
–
–
0
250
131
76
43
1
39
23
9
7
2
7
2
5
0
3
2
2
0
0
–
–
–
–
82 220
34 125
25 66
23 29
–
–
–
–
Yes
2
2
0
0
No
299
157
91
51
–
–
–
–
Yes
12
3
6
3
No
290
156
85
49
–
–
–
–
Yes
13
8
3
2
No
289
151
88
50
Extent of hepatic disease
Eastern Cooperative Oncology Group (ECOG) status
Previous hepatic resection Yes No Previous transarterial chemoembolization/ hepatic artery chemoinfusion
Prior ablation therapy
Concurrent chemotherapy
Child-pugh status
–
–
–
–
A (5–6) B (7–9)
282 4
150 2
85 0
47 2
C (10–15)
0
0
0
0
Unknown
16
7
6
3
Extrahepatic disease
–
–
–
–
Yes
124
58
44
22
No
178
101
47
30
–
–
–
–
Mean (±SD)
1.73 ± 0.44
1.76 ± 0.41
1.71 ± 0.46
1.73 ± 0.44
Range
0.44 – 2.55
–
–
– –
Radioembolization activity (Gbq)
Lung shunting (%)
–
–
–
Mean (±SD)
3.7 ± 2.7
4.0 ± 2.3
4.2 ± 2.4
4.4 ± 2.7
Range
0–20
–
–
–
Radioembolization of CRCLM
797
TABLE 1 continued Clinicopathological and treatment-related factors
All patients
Previous lines of chemotherapy 1
Preoperative blood parameters Bilirubin (mean ± SD)
2
[2
–
–
–
–
14.2 ± 16.3
14.0 ± 18.4
13.2 ± 9.7
14.2 ± 16.3
Albumin (mean ± SD)
38.9 ± 5.3
39.5 ± 5.1
39.7 ± 4.8
38.9 ± 5.3
Aspartate transaminase (AST) (mean ± SD)
44.6 ± 33.5
40.2 ± 31.1
46.4 ± 35.0
44.5 ± 33.4
Alanine aminotransferase (ALT) (mean ± SD)
35.9 ± 28.1
33.4 ± 25.0
38.8 ± 35.0
35.6 ± 28.1
Hemoglobin (Hb) (mean ± SD)
123.2 ± 18.0
125.1 ± 14.7
123.5 ± 16.6
123.2 ± 18.0
Platelet (Plt) (mean ± SD)
233.7 ± 110.5
228.5 ± 109.8
249.6 ± 120.0
233.7 ± 110.5
Creatinine (Cr) (mean ± SD)
73.4 ± 22.9
73.7 ± 109.8
73.4 ± 23.2
73.4 ± 22.9
time of treatment was 63.7 ± 11.0 years (range 28–88). The majority of patients presented with bilobar disease (n = 261, 86 %). The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 250 patients (83 %), 1 in 39 patients (13 %), 2 in 7 patients (2 %), and 3 in 2 patients (1 %). Twenty-six patients (9 %) had C51 % replacement of the liver by tumor. At study entry, 124 patients (41 %) had histologic or documented CT evidence of limited extrahepatic disease. Eighty-two patients (27 %) had previously undergone a liver resection. Two (1 %) patients had previously undergone transarterial chemoembolization or hepatic artery chemoinfusion; 12 patients (4 %) had previously undergone ablative therapy. One hundred fifty-nine (53 %) patients were previously treated with one line of systemic chemotherapy, 91 (30 %) were treated with two lines, and 52 (17 %) were treated with at least three lines. The mean dose of 90Y was 1.73 GBq (standard deviation [SD] = 0.44; range 0.44–2.55), and the estimated percentage shunting to the lungs was 3.7 % (SD = 2.7; range 0.0–20.0 %). One hundred forty-seven (49 %) patients required embolization of nonhepatic arteries to prevent nontargeted flow. Clinical Toxicity A total of 115 (38 %) patients developed clinical toxicity after treatment. Clinical toxicities included: nausea/ vomiting in 79 patients (26 %); nonspecific self-limiting abdominal pain in 54 patients (18 %); fatigue in 50 patients (17 %); anorexia in 24 patients (8 %); shortness of breath in 21 patients (7 %); gastritis in 4 patients (1 %); gastrointestinal ulceration in 1 patient (0 %); and radiationinduced lung disease in 1 patient (0 %). No patient had gallbladder or biliary complications as a result of treatment. Most complications (95 %) were minor and resolved without active intervention. Five (2 %) patients died within 30 days of treatment. Of these, two patients died from
suspected fatal pulmonary embolus, two patients died from clinical disease progression, and one patient died from radiation hepatitis. Postprocedural imaging findings demonstrated ascites and pleural effusion and in 9 (3 %) and 8 (3 %) patients each, respectively. A total of 16 (40 %) patients developed clinical toxicity after treatment. Clinical toxicities included: nausea/vomiting in 10 patients (25 %); nonspecific self-limiting abdominal pain in 8 patients (20 %); fatigue in 6 patients (15 %); anorexia in 2 patients (5 %); gallbladder and biliary-treerelated complications in 2 patients (5 %); and shortness of breath in 1 patient (3 %). These complications were minor (grade I/II) and resolved without active intervention. Postprocedural imaging findings demonstrated ascites, varices, pleural effusion, and pulmonary embolus in one patient (3 %) each, respectively. Splenic enlargement and drop in platelet count also are known complications after Y90 radioembolization; unfortunately, their incidence was not recorded in our prospective database. Treatment Response A total of 293 patients (97 %) were followed up beyond 2 months after initial radioembolization therapy and underwent follow-up CT imaging from which hepatic tumor response was assessed in accordance with RECIST criteria. Overall, a complete response to treatment was observed in 2 patients (of 302, 1 %), PR to treatment was observed in 111 patients (37 %), stable disease in 96 patients (32 %), and progressive disease (PD) in 84 patients (28 %). Response Stratified by Number of Previous Lines of Chemotherapy In patients who underwent one previous line of chemotherapy, complete/PR was observed in 69 patients (of 159, 43 %), stable disease in 46 (29 %), and PD in 41
798
A. Saxena et al. TABLE 2 Association of clinicopathological and treatment-related factors with overall survival on univariate analysis
100
Cumulative Survival %
90 80 70 60 50
Clinicopathological and treatment-related factors
Number of patients
Median survival (mo)
Total
302
–
Age at time of resection (year)
40 30
Median Survival = 10.5 months
20 10
n=302 0 0
6
12
18
24
30
36
42
48
54
60
66
72
Survival (months)
FIG. 1 Overall survival of 302 patients with CRCLM who underwent 90Y radioembolization
(26 %). In patients who underwent 2 previous lines of chemotherapy, complete/PR was observed in 32 patients (of 91, 35 %), stable disease in 34 (37 %), and PD in 22 (24 %). In patients who underwent three or more previous lines of chemotherapy, complete/PR was observed in 12 patients (of 52, 23 %), stable disease in 15 (29 %), and PD in 21 (40 %). This was significant on univariate analysis (p = 0.046). Overall Survival No patient was lost to follow-up; 216 (72 %) patients had died at the last time of follow-up. The median followup period for all patients after 90Y radioembolization was 7.2 months (range 0.2–72.8 months). The median survival after the first treatment with 90Y radioembolization was 10.5 months with 6-month and 12-, 18-, 24-, 30-, 36-, and 60-month survival of 66, 42, 29, 21, 17, 13, and 7 %, respectively (Fig. 1). Univariate analysis identified eight factors associated with overall survival: extent of replacement of hepatic parenchyma by tumor (\25 vs. 26–50 vs. C51 %, p \ 0.001); extent of hepatic disease (bilobar vs. unilobar, p = 0.028), number of previous lines of chemotherapy (1 vs. 2 vs. C3; p = 0.0.028), radiological response to treatment (CR/PR vs. SD vs. PD, p \ 0.001), preoperative AST (C45 vs.\45, p \ 0.001), preoperative ALT (C36 vs.\36, p = 0.002), preoperative hemoglobin (C123 vs. \123, p \ 0.001), and preoperative bilirubin (\14 vs. C14; p = 0.010). Table 2 demonstrates the significance of clinicopathological and treatment-related prognostic factors for overall survival. On multivariate analysis, poor radiological response to treatment (hazard ratio [HR], 4.0; 95 % confidence interval [CI],
p value
–
–
0.574
\64
145
9.9
–
C64
157
10.9
–
–
–
\0.001
0–25
163
11.6
–
26–50
97
9.1
–
51–75
26
5.6
–
–
–
0.028
Bilobar
261
9.8
–
Unilobar
41
15.9
–
–
–
0.523
Replacement of liver by tumor (%)
Extent of hepatic disease
Eastern Cooperative Oncology Group (ECOG) status 0–1
249
10.7
–
C2
48
8.7
–
Extrahepatic disease
–
–
0.100
Yes
177
11.6
–
No
124
8.8
–
–
–
0.304
81
12.0
–
Previous hepatic resection Yes No Number of previous lines of chemotherapy 1
220
9.8
–
–
–
\0.001
159
12.0
–
2
91
10.5
–
C3
52
5.6
–
–
–
0.123
Previous transarterial chemoembolization/hepatic artery chemoinfusion Yes
12
10.1
–
No
290
20.8
–
– 113
– 20.9
\0.001 –
Stable disease
96
10.1
–
Progressive disease
84
4.0
–
–
–
\0.001
\45
203
12.0
–
C45
81
5.2
–
–
–
0.002
\36
196
11.9
–
C36
96
8.0
–
–
–
\0.001
\123
132
6.6
–
C123
155
13.2
–
–
–
0.066
\74
159
9.0
–
C74
132
11.9
–
Radiological response Complete response/PR
Aspartate transaminase (AST)
Alanine aminotransferase (ALT)
Hemoglobin (Hb)
Creatinine (Cr)
Radioembolization of CRCLM
799
TABLE 2 continued
100
Median survival (mo)
p value
Bilirubin (Bi)
–
–
0.010
\14
197
11.3
–
C14
95
7.3
–
80 70 60 50 40
20
90
10
80
0
70
No extra-hepatic disease (n=177)
30
100
Extra-hepatic disease (n=124)
p=N.S
0
6
60
12
18
24
30
36
42
48
54
60
66
72
Survival (months)
50
FIG. 4 Overall survival, stratified by extrahepatic disease
40 30
0
p 2 lines (n=52)
0
6
12
18
24
30
36
42
48
54
60
66
72
Survival (months)
FIG. 3 Overall survival, stratified by number of previous lines of chemotherapy
3.20–4.96; p \ 0.001; Fig. 2), extensive replacement of hepatic parenchyma by tumor (HR 1.30; 95 % CI 1.02–1.66; p = 0.038; Fig. 3), number of previous lines of chemotherapy (HR 1.28; 95 % CI 1.05–1.56; p = 0.016), and low preoperative hemoglobin (HR 1.39; 95 % CI 1.03–1.86; p = 0.030) were associated with poorer prognosis.
In patients who underwent treatment with one previous line of chemotherapy, median survival was 12.0 months with a 6-month and 12-, 18-, 24-, 30-, 36-, and 60-month survival of 70, 49, 34, 27, 21, 18, and 10 %, respectively. In patients who underwent treatment with two previous lines of chemotherapy, median survival was 10.5 months with a 6-month and 12-, 18-, 24-, 30-, 36-, and 60-month survival of 69, 40, 27, 20, 14, 12, and 4 %, respectively. In patients who underwent treatment with at least three previous lines of chemotherapy, median survival was 5.6 months with a 6-month and 12-, 18-, 24-, 30-, 36-, and 60-month survival of 47, 21, 9, 9, 9, 0, and 0 %, respectively. This difference was significant on univariate (p \ 0.001) and multivariate analysis (p = 0.016). DISCUSSION In the past two decades, the introduction of new systemic and biologic agents combined with continuous
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refinements of existing chemotherapeutic regimens has improved the prognosis of patients with unresectable, chemo-naive CRCLM. Combined with 5-fluourouracil, irinotecan (FOLFIRI) and oxaliplatin (FOLFOX) have yielded objective response rates of 50–56 % and a median survival of 6.4–12.9 months in patients with metastatic, liver-dominant colorectal cancer.7–10 Between 4 and 37 % of patients are downstaged such that they may undergo a potentially curative surgical procedure.11,12 Nevertheless, many patients who have an initial robust response to first-line chemotherapy invariably develop disease progression and progress to a chemotherapyrefractory state. These patients have a median survival of only 4–6 months with best supportive care.13 Response rates for second and third-line systemic chemotherapies are dismal at between 5 and 25 %.14–16 The addition of biologic agents, such as bevacizumab, has shown some survival benefit in the chemorefractory setting, but further investigation is necessary.17,18 The optimal treatment for patients with advanced, unresectable, chemorefractory CRCLM is not defined. Our single-center study on 302 patients with chemorefractory CRCLM demonstrated a median survival of 10.5 months with a 24-month survival of 21 %. These data, in the context of what is otherwise a fatal disease process, are excellent. Most patients in our series presented with features of advanced disease, including a high incidence of extrahepatic disease, extensive liver disease, poor performance status, and progression of disease after multiple cycles of chemotherapy. In particular, 17 % had failed three or more lines of chemotherapy. Our results are commensurate with findings from previous smaller studies. Kennedy and colleagues evaluated the outcomes of 208 patients who underwent Y90 radioembolization between across seven institutions in the United States.19 The authors demonstrated a median survival of 10.5 months in patients who responded to treatment. Cosimelli and colleagues, in a prospective, multicenter phase II Italian trial, evaluated the outcomes of 50 patients treated with resin-based microspheres.10 The majority of patients had failed four or more lines of chemotherapy (76 %) and had extensive replacement (25–50 %) of liver by tumour (60 %). In this group of salvage patients, median survival was 12.6 months. Stubbs and colleagues reported an 11-month median survival in 100 patients with unresectable chemorefractory CRCLM.20 Overall, a careful analysis of the literature demonstrates that 90Y radioembolization of CRCLM is associated with a median survival of 8.3–36.0 months with a 2-year survival of 0–39 %. The lack of large, prospective, randomized data, however, has prevented this treatment from being more widely adopted.
A. Saxena et al.
Radiological response to treatment has been consistently identified as a strong prognostic factor; this also was observed in the current study.21,22 Median survival was 20.9 months in patients with CR/PR to treatment compared with only 4.0 months in patients with PD. Encouragingly, 39 % of patients had an objective response (CR/PR) to treatment. This is consistent with the 0–73 % objective response rate reported previously.20,23 Patient with extensive liver disease and previous treatment with multiple lines of chemotherapy (C3) had poorer prognosis. These data strongly suggest that 90Y radioembolization is more effective if used earlier in the treatment paradigm. Uniquely, our study showed that low pretreatment hemoglobin was a poor prognostic factor. Whilst low hemoglobin has been previously shown to portent a poorer outcome in patients undergoing a spectrum of procedures in surgical oncology, few if any studies have shown such an association after radioembolization.24 This unique finding warrants further investigation. Other studies have shown that poor performance status and the stage of cancer at diagnosis are associated with poorer outcomes.21 Extrahepatic disease also has identified as a potential prognosticator; our study, however, did not show a statistically significant association between limited extrahepatic disease and poor survival outcomes.20,25 Overall, whilst prognostic factors had been identified previously, there is still an urgent need to identify both the optimal candidates for 90Y radioembolization and those patients who are least likely to benefit. Other interventions have been evaluated as potential therapies for unresectable chemorefractory CRCLM. Bland transarterial embolization has been shown to be ineffective. The role of hepatic artery chemotherapy has been investigated in randomized trials; they have shown improved response rates with chemoperfusion (42–62 vs. 5–20 %), but only a few have showed an actual improvement in survival.26–28 A recent study by Kemeny and colleagues, however, analysed 49 patients with previously unresectable CRCLM who underwent hepatic-arterial infusion and systemic chemotherapy and showed that 47 % achieved conversion to resection at a median of 6 months after treatment initiation. These resectable patients had a 3-year survival of 80 %.29 Transarterial chemoembolization (TACE) represents a theoretic improvement on chemoinfusion by exposing tumors to higher concentrations of chemotherapy whilst minimising systemic toxicity. Several phase II studies have shown consistently higher response rates with TACE, but randomized studies are lacking and the impact on survival is still unclear.30–32 Recently, a Cochrane review concluded that there minimal evidence to support TAE/TACE in the metastatic setting.33
Radioembolization of CRCLM
An emerging alternative to Y90 radioembolization is drug-eluding beads impregnated with irinotecan (DEBIRI). The unique properties of the beads allows for fixed dosing and the ability to release chemotherapeutic agent in a sustained and controlled manner. This reduces systemic toxicity and theoretically improves tumor response. Initial evaluations of DEBIRI have demonstrated that it is safe and efficacious.34,35 Martin and colleagues reported a multi-institutional series of 55 patients who received DEBIRI after failing systemic chemotherapy.34 Response rate was 75 % at 12 months and overall survival in these patients was 19 months. Further data, however, is still required to determine the safety and efficacy of DEBIRI in the management of unresectable, chemorefractory CRCLM. 90Y radioembolization is safe. The median morbidity rate was 38 %; almost all complications were transient and resolved with medical therapy. Consistent with previous reports, fatigue, abdominal pain, and nausea/vomiting were the most frequent complications.36,37 Thirty-day procedural mortality was 2 %. These data are comparable to those reported in other studies, although a lack of standardization in the reporting of adverse events precludes a meaningful comparison. Whilst our study is the largest to evaluate the outcomes of patients with CRCLM undergoing 90Y radioembolization, it has several limitations. First, as a retrospective analysis of prospective databases, it is subject to the usual caveats of retrospective research. Second, our study lacks detailed information on the type of chemotherapeutic regimens used before, during and after radioembolization or the duration of therapy. These data would be useful. Similarly, our study lacks data on the site of extrahepatic metastases in patients before treatment. Third, our dataset does not contain information of biochemical toxicity or on the incidence of splenic enlargement or platelet drop, which are known complications of 90Y radioembolization. Finally, our dataset does not contain information on the site or date of hepatic and extrahepatic progression. Overall, despite limitations, our study demonstrates that 90Y radioembolization is a safe and effective treatment for unresectable, chemorefractory CRCLM. Given the absence of effective chemotherapeutic agents for this disease process and the uncertainty surrounding TACE, 90Y radioembolization should be considered a viable treatment for unresectable, chemorefractory CRCLM. Further prospective investigation, however, is still necessary. REFERENCES 1. GLOBOCAN 2012 V1.0 Cancer Incidence and Mortality Worldwide: IARC CancerBase No.11 2013. http://globocan.iarc. fr. Accessed 17 Aug 2014.
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