Abstract
There is conflicting literature regarding the superiority of transarterial chemoembolization (TACE) versus bland transarterial embolization (TAE), and this has not been well studied before transplantation. Twenty-five TAE patients were matched in a 1:2 ratio with TACE patients by the initial radiographic tumor size and number in a retrospective, case-controlled study. The patients were otherwise treated according to the same protocols. The method of embolization was chosen on the basis of interventionalist practices at 2 sites within the program. Kaplan-Meier survival analyses at 1 and 3 years were the primary endpoints. There were no significant demographic differences between the groups. The mean adjusted Model for End-Stage Liver Disease scores at transplantation and waiting times were not significantly different between the TAE and TACE patients (MELD scores: 26 ± 3 versus 24 ± 3 points, P = 0.12; waiting times: 13 ± 8 versus 11 ± 10 months, P = 0.43). TAE patients (16%) were less likely than TACE patients (40%) to require 2 procedures (P = 0.04). Explant tumors were completely necrotic for 36% of the TAE patients and for 26% of the TACE patients. The 3-year overall survival rates were 78% for the TAE patients and 74% for the TACE patients (P = 0.66), and the 3-year recurrence-free survival rates were 72% for the TAE patients and 68% for the TACE patients (P = 0.67). On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83). In conclusion, there were no significant differences in wait-list dropout or in overall or recurrence-free survival between HCC patients undergoing TAE and HCC patients undergoing TACE before transplantation.
Liver transplantation is the standard of care for select patients with hepatocellular carcinoma (HCC) and cirrhosis. In response to high rates of recurrence and poor overall survival in the early years of transplantation, guidelines for transplantation for patients with HCC were developed. Most transplant centers in the international community use the Milan criteria to assess the candidacy of HCC patients for liver transplantation.1 The 5-year survival rate for these patients exceeds 70%.
Although the 5-year survival rate is robust for transplant patients within the Milan criteria, wait-list dropout remains a significant concern because of limited organ availability. HCC progression correlates with time, as does the risk of dropout from the wait list for medical and/or psychosocial reasons. Dropout rates range from 0% to 10% at 12 months according to cohort studies of T2 tumor patients from the last decade; rates as high as 40% at 12 months were previously reported.2,3 One response has been the supplementation of Model for End-Stage Liver Disease (MELD) points for HCC based on the projected risk of tumor expansion beyond the Milan criteria. The United Network for Organ Sharing (UNOS) offers MELD exception points to patients who have tumors within the Milan criteria or whose tumors have been downsized by locoregional therapy to meet these criteria. However, in the United States, the benefit of MELD exception points varies by UNOS region.4 Currently, 767 of 16,878 candidates listed for liver transplantation have a primary diagnosis of HCC. Twenty-five percent of these candidates have been listed for more than 1 year, and 53% have been waiting for longer than 6 months (according to Organ Procurement and Transplantation Network data as of April 20, 2012).
Another strategy used to prevent progression on the wait list has been the use of embolic or ablative therapies. Among the available therapies, transarterial chemoembolization (TACE) has been used for more than a decade, and it is recommended by guidelines from both the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.5–9 Bridging strategies with the aim of tumor destruction are considered to be beneficial for T2 patients waiting longer than 6 months. Both TACE and bland transarterial embolization (TAE) induce tumor necrosis at rates in the range of 16% to 60%.10,11 TACE remains the more common practice while patients are awaiting transplantation despite the absence of convincing evidence of its superiority, and recognized toxicities.
To provide further insight, we performed a retrospective, matched case-control study of patients undergoing TAE and TACE while awaiting transplantation. Equivalency between treatments was hypothesized.
PATIENTS AND METHODS
Patient Evaluation and Management
The transplantation program provided care for candidates at 2 quaternary academic medical centers with more than 800 beds each. The same written protocols were used for patient evaluation and selection and postoperative management and surveillance. All patients were evaluated by a multidisciplinary team at the respective medical centers and were presented to a cross-campus selection committee; transplant hepatologists and surgeons cross-covered both medical centers. Patients with HCC were reviewed at a weekly conference of hepatologists, transplant surgeons, and diagnostic and interventional radiologists at which cross-sectional imaging was reviewed. All patients with appropriate hepatic reserves underwent bridging therapy if they were listed within the Milan criteria or if they met the University of California San Francisco (UCSF) criteria.12 The determination of whether to pursue embolization or ablation was based on a consensus reached at the weekly conference. Because of institutional preferences, interventional radiologists at center A performed TACE, whereas interventional radiologists at center B performed TAE. All procedures were performed by interventional radiologists who were board-certified in diagnostic radiology, and fellowship-trained in interventional radiology at major transplantation centers. Because both centers were major referral centers for gastrointestinal disease and cancer, the interventional radiologists were very experienced with locoregional therapies.
Scans were repeated approximately 1 month after an intervention and reviewed at conference to assess the need for further therapy, and they were repeated at 3-month intervals thereafter. During this study period, all transplant operations occurred at center A, and center A pathologists evaluated all specimens. Nonsurgical postoperative care and long-term HCC surveillance were conducted at each patient’s preoperative medical center. Therefore, the major difference in the care received by patients with HCC between the 2 medical centers was the interventional radiology procedure performed.
Intention-to-Treat Analysis
All patients who underwent HCC embolization and were actively listed at centers A and B during the period of February 2002 to October 2010 were included in an intention-to-treat analysis with the Fine and Gray method for competing events. The entry date was the date of first embolization, and the treatment was defined as transplantation.
Case-Control Groups, Measures, and Analyses
A retrospective case-control study was performed. A review of a prospective database of all patients evaluated for liver transplantation was performed to identify patients with explant-confirmed HCC who had undergone bridging with transarterial therapies between February 2002 (the date of acceptance of the Milan criteria by UNOS) and October 2010; the first case meeting this criteria was performed in May 2002. A total of 25 patients with HCC were successfully bridged to transplantation with TAE. These patients were matched to transplant patients with explant-confirmed HCC after TACE during the same period in a 1:2 ratio according to the initial radiographic tumor size and number of tumors. Because the 25 TAE patients had unilobar disease at diagnosis, TACE patients with bilobar disease at diagnosis were excluded from the match to increase uniformity. The embolization decision was based on the tumor size, location, number, and the degree of underlying liver disease, with a total bilirubin level of 3 mg/dL usually serving as the cutoff for safe embolization.
The primary outcome measures were overall patient survival and recurrence-free survival. Overall survival was defined as the time from first embolization to death or last follow-up. Recurrence-free survival was defined as the time from first embolization to the recurrence of HCC after transplantation or death. Analyses are reported for 1 and 3 years because a small number of patients at center B had more than 4 years of data. Secondary outcome measures included the number of distinct embolization procedures and tumor necrosis according to explant pathology.
Continuous variables are reported as means and standard deviations or as medians and interquartile ranges, and they were compared with the Student t test or Mann-Whitney-Wilcoxon test. To compare categorical variables, we used Pearson’s χ2 test or Fisher’s exact test. Time-to-event analyses were performed with the Kaplan-Meier method and the log-rank test. Repeated measures logistic regression was performed to assess longitudinal changes in tumors based on imaging and pathology and the Milan and UCSF criteria over time. A P value ≤0.05 was considered to indicate a statistically significant result. The institutional review board approved this protocol. Data were analyzed with Stata 11.2 (StataCorp, College Station, TX).
RESULTS
Population
During the study period, 1717 candidates in all from centers A and B were listed for transplantation, and 374 (22%) carried a primary or secondary diagnosis of HCC. A total of 256 listed patients underwent TAE (12%) or TACE (88%). Two hundred twenty of these patients underwent transplantation, 28 patients were delisted, and 8 patients were awaiting transplantation at the end of the period or were transferred to another center. The reasons for wait-list dropout are detailed in Table 1. Notably, 61% of the embolized patients who dropped off the wait list did so because of HCC progression or HCC-related death. On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83).
TABLE 1.
Wait-List Dropout Among All Patients With HCC Who Were Listed for Transplantation Between February 2002 and October 2010
| Reason for Dropout | Patients
|
|
|---|---|---|
| n = 25 | n = 3 | |
| Death due to complications of liver failure [n (%)] | 1 (4) | |
| Death due to HCC progression [n (%)] | 6 (24) | |
| HCC progression [n (%)] | 10 (40) | 1 (33) |
| Too sick for transplantation [n (%)] | 8 (32) | 2 (67) |
Demographics for Case-Control Analyses
The study population was primarily male (n = 62 or 83%) and Caucasian (n= 38 or 51%) and had a median age of 59 years (interquartile range = 42–69 years); there were no significant demographic differences between the TAE and TACE groups. Hepatitis C virus was the most common etiology for the underlying liver disease (Table 2). The mean laboratory MELD scores at transplantation were 9 ± 6 (median = 8, interquartile range = 3–16) for the TAE group and 10 ± 5 (median = 9, interquartile range = 4–17) for the TACE group (P = 0.41). The mean MELD scores at transplantation with exception points were 26 ± 3 (median = 25, interquartile range = 22–28) for the TAE group and 24 ± 3 (median = 22, interquartile range = 22–28) for the TACE group (P = 0.42). Sixty percent of the patients had MELD exception points: 17 TAE patients (68%) and 28 TACE patients (56%; P = 0.32) at the time of transplantation. Nine TAE patients (38%) and 27 TACE patients (55%) received transplants making use of extended-criteria grafts (P = 0.16).
TABLE 2.
Characteristics of 25 Patients Undergoing TAE and 50 Patients Undergoing TACE Who Were Matched by Tumor Size and Number on Initial Diagnostic Imaging: May 2002 to October 2010
| TAE Group (n = 25) | TACE Group (n = 50) | P Value | |
|---|---|---|---|
| Demographics | |||
| Age (years) | 58 ± 8 | 57 ± 11 | 0.80 |
| Sex: male [n (%)] | 22 (88) | 40 (80) | 0.39 |
| Race [n (%)] | |||
| White | 13 (52) | 25 (50) | 0.45 |
| Hispanic | 4 (16) | 14 (28) | |
| Black | 3 (12) | 2 (4) | |
| Other | 5 (20) | 9 (18) | |
| Underlying liver disease [n (%)] | |||
| Hepatitis C virus | 22 (88) | 35 (70) | 0.15 |
| Other | 3 (12) | 15 (30) | |
| Diagnostic labs | |||
| Total bilirubin (mg/dL) | 1.5 ± 1.3 | 1.8 ± 1.2 | 0.46 |
| Platelets (109/L) | 121 ± 143 | 105 ± 113 | 0.60 |
| International normalized ratio | 1.22 ± 0.32 | 1.26 ± 0.21 | 0.58 |
| Alpha-fetoprotein ≥200 μg/L [n (%)] | 4 (16) | 8 (16) | 1.0 |
| MELD score at transplantation | |||
| Laboratory score | 9 ± 6 | 10 ± 5 | 0.41 |
| Exception points | 26 ± 3 | 24 ± 3 | 0.42 |
| Patients with exception points [n (%)] | 17 (68) | 28 (56) | 0.32 |
| Months to transplantation | |||
| Radiographic diagnosis | 13 ± 8 | 11 ± 10 | 0.39 |
| First embolization | 8 ± 5 | 6 ± 7 | 0.34 |
| Listing | 10 ± 16 | 6 ± 8 | 0.40 |
The mean time from the radiographic diagnosis to transplantation was 13 ± 8 months for the TAE group and 11 ± 10 months for the TACE group (P = 0.43); the study median was 9 months (interquartile range = 6–15 months; Table 3). The 2 groups were matched by tumor size and number (Table 3): the mean number of tumors was 1.5 ± 0.7 for the TAE group and 1.4 ± 0.6 for the TACE group, and the largest tumor was 2.7 ± 1.7 cm for the TAE group and 2.7 ± 1.6 cm for the TACE group. At the time of the radiographic diagnosis, 18 TAE patients (72%) and 34 TACE patients (68%) were within the Milan criteria (P = 0.72); 2 TAE patients (8%) and 3 TACE patients (6%) were within the UCSF criteria (P = 0.74); and the remainder were outside these criteria. More specifically, 1 tumor was beyond the UCSF criteria, and the 17 remaining lesions were too small to meet the Milan criteria.
TABLE 3.
Tumor Characteristics and Embolization Details for 25 Patients Undergoing TAE and 50 Patients Undergoing TACE Who Were Matched by Tumor Size and Number on Initial Diagnostic Imaging: May 2002 to October 2010
| TAE Group (n = 25) | TACE Group (n = 50) | P Value | |
|---|---|---|---|
| Radiographic tumor characteristics at diagnosis | |||
| Number of tumors [n (%)]* | |||
| 1 | 15 (60) | 33 (66) | 0.79 |
| 2 | 8 (32) | 14 (28) | |
| ≥3 | 2 (8) | 3 (6) | |
| Largest tumor diameter [n (%)]* | |||
| <2 cm | 9 (36) | 18 (36) | 1.0 |
| 2–5 cm | 14 (56) | 28 (56) | |
| >5 cm | 2 (8) | 4 (8) | |
| Within Milan criteria [n (%)] | 18 (72) | 34 (68) | 0.72 |
| Within UCSF criteria [n (%)] | 2 (8) | 3 (6) | 0.74 |
| Arterial embolization | |||
| Procedures before transplantation [n (%)] | |||
| 1–2 | 24 (96) | 48 (96) | 0.19 |
| 3–4 | 1 (4) | 2 (4) | |
| Pharmacological embolization at first intervention [n (%)] | |||
| Adriamycin, cisplatin, mitomycin | 0 | 47 (94) | |
| Adriamycin | 0 | 3 (6) | |
| Ethiodol | 1 (4) | 40 (80) | |
| Radiographic tumor characteristics at transplant | |||
| Number of tumors [n (%)] | |||
| 1 | 12 (48) | 35 (70) | 0.11 |
| 2 | 10 (40) | 9 (18) | |
| ≥3 | 3 (12) | 6 (12) | |
| Largest tumor diameter [n (%)] | |||
| <2 cm | 7 (28) | 16 (32) | 0.89 |
| 2–5 cm | 13 (52) | 23 (46) | |
| >5 cm | 5 (20) | 11 (22) | |
| Bilobar [n (%)] | 2 (8) | 4 (8) | 0.96 |
| Within Milan criteria [n (%)] | 19 (76) | 34 (68) | 0.45 |
| Within UCSF criteria [n (%)]† | 1 (4) | 2 (4) | |
| Explant tumor characteristics | |||
| Number of tumors [n (%)] | |||
| 1 | 15 (60) | 36 (72) | 0.51 |
| 2 | 6 (24) | 7 (14) | |
| ≥3 | 4 (16) | 7 (14) | |
| Largest tumor diameter [n (%)] | |||
| <2 cm | 9 (36) | 14 (28) | 0.77 |
| 2–5 cm | 11 (44) | 24 (48) | |
| >5 cm | 5 (20) | 12 (24) | |
| Complete tumor necrosis [n (%)] | 9 (36) | 13 (26) | 0.37 |
| Bilobar [n (%)] | 4 (16) | 5 (10) | 0.45 |
| Within Milan criteria [n (%)] | 14 (56) | 24 (48) | 0.69 |
| Within UCSF criteria [n (%)]† | 1 (4) | 3 (6) | |
| Documented HCC recurrence after transplant [n (%)] | 3 (12) | 9 (18) | 0.50 |
Matching criteria.
The data were too few for meaningful statistical comparisons.
The time from first embolization to transplantation was 8 ± 5 months for the TAE group and 6 ±7 months for the TACE group (P = 0.34). The overwhelming majority of the patients underwent a single transarterial procedure, with 16% of the TAE group (n = 4) and 40% of the TACE group (n= 20) undergoing 2 procedures and with 4% of the TAE group (n = 1) and 2% of the TACE group (n= 1) undergoing 4 procedures. Superselective embolization occurred during the first embolization procedure in 76% of the TAE cases (19/25) and in 92% of the TACE cases (45/49; P = 0.06), during the second embolization procedure in 75% of the TAE cases (3/4) and in 74% of the TACE cases (14/19; P = 0.12), during the third embolization procedure in 100% of the TAE cases (1/1) and in 100% of the TACE cases (2/2), and during the fourth embolization procedure in 100% of the TAE cases (1/1) and in 100% of the TACE cases (1/1). There were 2 crossovers from TAE to TACE, and there were no crossovers from TACE to TAE. One crossover occurred during the second chemoembolization, and the other occurred during the third chemoembolization; a clear rationale could not be determined for one of the patients, and the second patient was an inpatient at center A, which routinely performed TACE. All repeat embolizations treated local unilobar tumor recurrence except for 2 patients in the TACE group and 1 patient in the TAE group for whom new bilobar disease was treated.
The particle size used for vessel stasis was identified for 97% of the 31 TAE interventions: 40 to 120 μm for 5 procedures (17%), 40 to 120 μm combined with 100 to 300 μm for 5 procedures (17%), 100 to 300 μm for 18 procedures (60%), and 300 to 500 μm for 2 procedures (6%). Ethiodol was used once (3%). The particle size used for vessel stasis was identified for 85% of the 73 TACE interventions: 40 to 120 μm for 3 procedures (6%), 100 to 300 μm for 54 procedures (87%), and 300 to 500 μm or larger for 5 procedures (7%). Adriamycin-based therapy was used for 100% of the total TACE procedures, and Ethiodol was used for 94% of these procedures.
According to the imaging closest to transplantation, there were no significant differences in the tumor number or size (Table 3): the mean number of tumors was 1.6 ± 0.8 for the TAE group and 1.3 ± 0.8 for the TACE group (P = 0.11), and the largest tumor was 2.9 ± 1.4 cm for the TAE group and 3.1 ± 2.2 for the TACE group (P = 0.89). Eight percent of the patients in both groups now had bilobar disease (P = 0.96). Nineteen of the TAE patients (76%) and 34 of the TACE patients (68%) were within the Milan criteria (P = 0.45), and 1 member of the TAE group (2%) and 2 members of the TACE group (4%) were within the UCSF criteria. More specifically, 9 tumors were beyond the UCSF criteria, and 10 lesions remained too small to meet the Milan criteria.
At explant, 14 of the TAE patients (58%) and 24 of the TACE patients (53%) were within the Milan criteria (P = 0.69); 1 patient in the TAE group (4%) and 3 patients in the TACE group (6%) were within the UCSF criteria (Table 3). The mean number of tumors was 1.9 ± 1.7 for the TAE group and 1.4 ± 1.1 for the TACE group (P = 0.51), and the largest tumor was 2.8 ± 1.8 cm for the TAE group and 3.3 ± 2.6 cm for the TACE group (P = 0.77).
Longitudinal Analyses
Patients were followed with serial imaging from the time of diagnosis through embolization and were compared on the basis of explant pathology. During the study period, 73% of the patients radiographically diagnosed within the Milan criteria remained within the Milan criteria according to explant findings. Moreover, 61% of the patients not diagnosed within the Milan criteria remained outside the Milan criteria at transplant. As for the UCSF criteria, 29% of the patients radiographically diagnosed within the UCSF criteria remained so according to explant findings. Moreover, 96% of the patients not diagnosed within the UCSF criteria remained outside the UCSF criteria at transplant. Transitions into or out of the Milan (P = 0.48) or UCSF criteria (P = 0.24) were not significantly different between the TAE and TACE groups.
Survival and Recurrence-Free Survival Analyses
The rates of overall survival from the date of first embolization to death for transplant patients undergoing TAE were 96% (range = 75%–99%) and 78% (range = 55%–90%) at 1 and 3 years, respectively (Fig. 1). The rates of overall survival from the date of first embolization to death for transplant patients undergoing TACE were 94% (range = 82%–98%) and 74% (range = 59%–85%) at 1 and 3 years, respectively. There was no significant difference (log-rank P = 0.66). The rates of recurrence-free survival from the date of first embolization to HCC recurrence for transplant patients undergoing TAE were 91% (range = 70%–98%) and 72% (range = 48%–87%) at 1 and 3 years, respectively (Fig. 2). The rates of recurrence-free survival from the date of first embolization to HCC recurrence in transplant patients undergoing TACE were 92% (range = 80%–97%) and 68% (range = 51%–80%) at 1 and 3 years, respectively. There was no significant difference (log-rank P = 0.67).
Figure 1.
Overall survival of patients with HCC undergoing liver transplantation after TAE or TACE bridging therapy from the date of first embolization.
Figure 2.
Recurrence-free survival of patients with HCC undergoing liver transplantation after TAE or TACE bridging therapy from the date of first embolization.
DISCUSSION
Hepatic artery embolization of HCC is a validated palliative therapy for the treatment of patients with tumors too large to be treated by liver transplantation or too decompensated to be treated with resection. Transarterial therapy as a bridging therapy is supported by internationally recognized guidelines when the wait time exceeds 6 months.8,9 As Seehofer et al.13 recently summarized, transarterial therapy theoretically promotes control of tumor growth and vascular invasion, mitigates dropout during the waiting period, induces tumor necrosis to reduce tumor dissemination during transplantation, down-stages patients, and improves posttransplant outcomes by reducing the recurrence risk. These assertions come from the experiences of individual centers. In the current series, the mean time from the radiographic diagnosis to transplantation was 12 months, and this justified the program’s tumor control strategy.
With liver transplantation considered the intended treatment, an intention-to-treat analysis demonstrated no statistical difference between TACE and TAE as bridging therapies for the population of patients undergoing embolization for HCC. In other words, wait-list dropout due to progression or death related to HCC was not affected by the transarterial modality used at centers A and B. After matching for tumor size and number, no significant differences in the primary endpoints were identified for patients undergoing TACE and TAE. The overall 3-year survival rates were 78% and 74% for transplant patients undergoing TAE and TACE, respectively, and the 3-year recurrence-free survival rates were 72% and 68% for transplant patients undergoing TAE and TACE, respectively. In both groups, overall survival and recurrence-free survival were concordant with expected outcomes for patients within the Milan and UCSF criteria.8,9,14,15
As a proxy of tumor progression or regression with respect to the embolization modality, longitudinal analyses were performed to assess movement along a continuum from T1 tumors (below the Milan criteria) to T2 tumors (the Milan criteria) to the UCSF criteria and beyond the UCSF criteria. There was movement within these groups from diagnostic imaging through postembolization imaging and explant pathology, but no significant differences were observed according to the use of TAE or TACE. Some of this movement may have been related to imaging, which has been demonstrated to both understage and overstage lesions in the range of 10% to 22%.1,16–18
Both TAE and TACE induce tumor necrosis in up to 50% of treated patients, with objective responses noted in 16% to 60% of treated patients on cross-sectional imaging.9,19 The literature is conflicting about whether the addition of chemotherapeutics to the embolization agent enhances antitumoral effects, especially because there is currently no uniformity in agents, doses, or delivery mechanisms.8,9,20 All explants were examined for tumor necrosis in the current study, and complete tumor necrosis was noted in 29% of the patients overall, with 36% in the TAE group and 26% in the TACE group (P = 0.37). Pathological reporting of partial necrosis was not uniform, so this was not included.
These findings are reinforced by the American Association for the Study of Liver Diseases guidelines, which state that there are no differences between TAE and TACE.9 In contrast, the European Association for the Study of the Liver guidelines, based on the same literature, discourage the use of TAE.8 In a meta-analysis including 6 randomized controlled trials (3 of which directly compared TAE and TACE), TAE and TACE were found to be superior to the control. However, a sensitivity analysis showed a significant survival benefit with TACE versus the control but not with TAE.19 The authors cautioned that this may have been an effect of the sample size, and in their multicenter randomized control trial of TACE, TAE, and symptomatic management that was published 1 year later, they concluded that the results might have shifted the meta-analysis of TAE if it had been performed again.10 In that study, TAE showed an advantage over the control, but the study was terminated before conclusive data could be collected. Other studies comparing TAE and TACE and also including drug-eluting beads, which are believed to provide controlled and sustained cytotoxic delivery, have also failed to demonstrate the superiority of TACE.20,21
Neither center performed scheduled repetitive treatments. Repeat embolization was performed only for de novo lesions or when 1-month postembolization imaging showed residual disease. The average number of retreatments was consistent with historical reports in the range of 2 to 5.9,10,18,19 However, patients receiving TACE were more than twice as likely to require 2 interventions. Underlying hepatic reserves based on total bilirubin levels and international normalized ratios were not significantly different between the groups, so an approach to prevent decompensation in the TACE patients with less aggressive first embolization does not explain this difference.22 The trend toward fewer procedures in the TAE group may have cost implications: a recent study based on detailed Medicare costs from the Surveillance, Epidemiology, and End Results database estimated the cost per TACE procedure to be $24,304.23 Although we are unable to provide head-to-head cost data, embolization procedures are clearly costly, and fewer procedures would represent a cost reduction strategy.
This study had limitations outside those related to its retrospective design. Pathology reports did not uniformly comment on the degree of tumor necrosis when multiple lesions were present. Therefore, tumor necrosis was reported in this analysis only when complete necrosis of all lesions was observed. The sample size was another potential limitation of this investigation. Center B contributed a smaller number of patients to the overall program volume, so there were case data for only 25 TAE patients. Although it can be argued that this limited the power to make a decision about therapy equivalency, the sample size was not remarkably different from the sample sizes of other studies informing decision making in this area.8,9,11 Because of the disagreement in the literature about the long-term efficacy of TAE and TACE with respect to survival and recurrence-free survival, these findings cannot be generalized to patients not being bridged to transplantation within approximately a year of their diagnosis. Although other center biases may exist, they should be no more significant than those that would be observed in any multicenter study: all interventions were performed by highly trained and experienced specialists treating patients cared for and monitored by a single multidisciplinary team.
In conclusion, the current study makes an important contribution to the literature by suggesting equivalency between TACE and TAE as bridges to transplantation.
Acknowledgments
The authors thank William Brubaker and Jonah Zaretsky for their efficient and accurate data collection efforts.
Abbreviations
- HCC
hepatocellular carcinoma
- MELD
Model for End-Stage Liver Disease
- TACE
transarterial chemoembolization
- TAE
transarterial embolization
- UCSF
University of California San Francisco
- UNOS
United Network for Organ Sharing
Footnotes
The authors of this article have no conflicts of interest to disclose as described by Liver Transplantation, and no funding was received.
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