Abstract
Background/Aim: To retrospectively evaluate the efficacy and safety of drug eluting bead (DEB) transarterial chemoembolisation (TACE) with microspheres <150 μm for the treatment of hepatocellular carcinoma (HCC) with respect to overall survival, progression-free survival, tumor response and the peri-interventional toxicity. Materials and Methods: In this retrospective, single-center study we analyzed 32 HCC-patients (BCLC A: 10 patients, BCLC B: 17 patients, BCLC C: 5 patients), who were treated with (DEB) <15 μm (DCBeadM1®) loaded with epirubicin between 2011 and 2015. We analyzed MRI and CT-scans as well as blood results like AFP, bilirubin and liver enzymes before (t0) and after (t1=first follow-up, t2=last follow-up within 6 months) locoregional treatment. The tumor response was evaluated by MRI and CT considering m-RECIST and the EASL-criteria as well as alpha-fetoprotein (AFP) levels in the peripheral blood. Results: We found a significant tumor response at all follow-up times (p<0.05) according to m-RECIST criteria and a significant tumor response between t0 vs. t1 (p<0.05) and t0 vs. t2 (p<0.05) according to EASL criteria. We observed a significant decrease of the AFP-level between t0 and t1. The objective response rates (ORR) of target lesions were 64.3% and 78.5 % corresponding to m-RECIST and EASL, respectively. The median overall survival (OS) was 30.5 months, the progression-free survival in relation to the target lesion was 14.3 months by using m-RECIST and EASL criteria. In the period of 30 days after treatment we found no grade 5 adverse events (AE). During the follow-up period 1 abscess (3.7%) was observed. In a total of 5 patients, 4 (14.7%) biliomas with no need of treatment and 3 (10.7%) widening of the intrahepatic bile ducts were noted. Conclusion: The use of DEB <150 μm (DCBeadM1®) shows promising results in the treatment of HCC without showing substantial hepatic toxicity, but some widening of the intrahepatic bile ducts and one abscess. Further trials are necessary to evaluate the efficacy and toxicity of DEB-TACE with M1®-beads.
- HCC treatment
- drug eluting bead
- transarterial chemoembolisation
- microspheres <150 μm
- toxicity
- survival
- DEB
- TACE
Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and accounts for more than 90% of liver cancers (1, 2). There has been a marked increase in HCC-related annual death rates during the past two decades, with the majority of all cases of HCC worldwide found in the Asia–Pacific region (3). In the United States, the incidence of HCC has increased since the 1980s as well (4). Thus, HCC represents a major public health problem. Unfortunately, only few HCCs are detected in an early stage of the disease, which implies that most patients do not qualify for potentially curative treatment options like transplantation, surgical resection and thermal ablation. Therefore, palliative treatment options like drug eluting bead transarterial chemoembolisation (DEBTACE) are of increasing importance and have been further investigated und improved in the recent years with the result of an increased overall survival. Transarterial chemoembolisation with drug eluting beads is a well-developed and established technique that combines an arterial occlusion and an exposure of high drug concentrations to the targeted tumor. In contrast to normal liver parenchyma, the hepatocellular carcinoma has a predominant arterial blood supply. Smaller size beads can reach into smaller tumor feeding vessels with a potentially superior efficacy and increased necrosis of the target tissue. However, there is supposed to be an increased rate of adverse events with respect to the intrahepatic biliary system because of a higher risk of ischemia of the peribiliary plexus caused by the small beads.
Materials and Methods
Study design and patients. We retrospectively analysed 32 HCC-patients (BCLC A: 10 patients, BCLC B: 17 patients, BCLC C: 5 patients), who were treated by DEBTACE with beads <150 μm and at least 6 months of follow-up. Patients that were downstaged to curative treatment like thermal ablation were excluded as well as patients that underwent neither follow-up CT nor MRI-scans. One patient with an extraordinary high AFP-value was also excluded.
DEBTACE. To deliver the drug eluting beads we utilized an angiografic system (Axiom ArtisZee, Siemens, Germany) and a transfemoral arterial approach by using a 4F or 5F sheath and a corresponding catheter with a cobra- or SIM-1-configuration. After displaying the superior mesenteric artery (SMA) to verify or rule out blood supply to the liver and to obtain an indirect portography we intubated the common hepatic artery via the celiac axis and performed a power-injected DSA-run for mapping the intrahepatic arterial tree. Routinely a contrast enhanced cone-beam CT was performed to rule out aberrant flow into the GI-tract, to identify the tumor feeding arteries and confirm the complete coverage of tumors from the anticipated treatment positions. Tumors are usually identified by their characteristic arterial tumor blush. For the superselective approach of the tumor feeding arteries either 2,4F or 2,7F microcatheters were used. After confirmation of the superselective treatment position Epirubicin-loaded DCBeads®M1 (Biocompatibles, Farnham, Surrey, UK) were administered. The procedure was repeated for every tumor-feeding artery, always taking care of not embolising non-target areas in order to avoid toxicity to non tumor-baring liver tissue. A non-selective embolisation from the proper hepatic artery was never performed. Finally, all material was removed and haemostasis was achieved by compressing the groin.
Pre- and post-treatment work-up. CT images were obtained by using a multi-detector–row CT scanner (Somatom Sensation 16, Siemens, Germany). We used a three-phase protocol with a native scan, an arterial phase scan 10sec and a portal-venous phase scan 45sec after administration of 100ml contrast medium (Imeron300, Bayer, Germany). Beside axial images, we used coronal and sagittal reconstructions with a slice thickness of 5 mm for the image analysis. The acquisition was done with a FOV of 300, 180mAs, 120kV, a pitch of 0,75.
For MRI a 1,5T system (Magnetom Aera, Siemens, Germany) with an abdominal-surface-coil was used. A hepatocyte-specific contrast agent (Primovist®, Bayer, Germany) was applied and the following sequences obtained: T2w-haste axial and coronal in breath-hold-technique, DWI axial, a t1w-3d-gradientecho-sequence (VIBE Dixon) native and dynamic (arterial, portalvenous, equilibrium and hepatocyte-specific phase after 20 min).
Each patient underwent an examination before (baseline) and at least two after (follow-up) the first DEBTACE. We used the m-RECIST and EASL-criteria for imaging analysis. Considering the tumor response, we distinguished between target response and overall-response in case of multiple lesions. All cases of complete and partial response were grouped in the overall response rate (ORR) group. Considering RECIST target response means the comparison of maximal two treated lesions with contrast uptake in contrast to EASL that includes all embolised lesions with contrast uptake. The ORR includes new tumor lesions in intra- and extrahepatic tissue.
Complete response (CR) and partial response (PR) were considered as treatment-response, stable disease (SD) and progressive disease (PD) as non-response.
AFP, as an established blood parameter in the follow-up of HCC, was examined before and after DEBTACE. The normal level of AFP was <=20 ng/ml. Patients with AFP-decrease compared to baseline were considered AFP-responders, all others were non-responders.
To review adverse events, we employed the Common Criteria of Adverse Events Version 4.0 (CTCAE). To evaluate liver toxicity blood samples were analysed for glutamic-oxaloacetic transaminase (GOT) (norm:10-35U/l), glutamate-pyruvate-transaminase (GPT) (norm:10-45U/l), gamma-glutamyltransferase (GGT) (norm:9-55U/l) and alkaline phosphatase (AP) (norm: 0.1-1.0 mg/dl) levels.
By using MRI, we compared the width of the bile ducts before and after DEBTACE to evaluate biliary toxicity. If there was a widening of the intrahepatic bile ducts compared to the baseline image, we distinguished between a modest increase (diameter of bile duct < accompanying portal vein) and moderate increase (diameter of bile duct > accompanying portal vein). In addition, we considered post interventional biliomas (area of fluid in transversal images > 1cm without contrast uptake) as adverse event of biliary toxicity.
Statistical analysis. Cumulative overall survival curves were generated by the Kaplan-Meier method. The date of death was defined as an event. In the case of drop out of a patient during the follow-up, the last contact data or in the other cases the last date of examination during the follow-up-period was censored. Every suitable parameter with influence on the survival time was evaluated by the logrank-test. A p-value of less than 0.05 was considerate indicating a significant difference. The statistical analysis of blood parameters was evaluated with the Friedmann-test for connected, non-parametric data.
All statistical analyses were evaluated by using Sigmaplot 2004 for Windows, version 9.0 with SigmaStat 3.1 Integration.
Results
The study included 32 patients, 4 female and 28 male. A total of 19 patients (59.4%) were Child-Pugh-A, 12 patients (12%) Child-Pugh-B and 1 patient (3.1%) Child-Pugh-C. According to the BCLC staging and treatment system 10 patients (31.3%) were BCLC-A, 17 (53.1%) BCLC-B and 5 (15.6%) BCLC-C, respectively. All BCLC-C patients were categorised in this group because of their impaired ECOG performance status and not because of the liver function or tumor characteristics.
The time between first diagnosis and treatment by DEBTACE was 14 days (median). Each patient was presented and discussed in a multi-disciplinary tumor board. The average number of DEBTACE sessions during the 6 months follow-up period was 2 (min 1, max 6). 4 patients were lost to follow-up after first follow-up imaging. Follow-up imaging by MRI was performed every 6 weeks (median 41 days).
Survival. The median overall survival was 914 days (30.5 months). The progression free survival (PFS) was defined as the period between the first DEBTACE and occurrence of tumor progression or death (censored). The PFS for target lesions was 14.3 months (m-RECIST and EASL) compared to PFS for all lesions (treated sequentially by DEBTACE) with 10.7 months (m-RECIST and EASL).
Considering the BCLC-A, -B and -C patients, we found a median survival time of 616 days (20.5 months), 805 days (26.8 months) and 228 days (7.6 months), respectively without a significant difference in the log-rank test.
Even in the subgroup analysis of other depending factors (Child-Pugh-Score, Baseline AFP, single/multifocal tumor, number of DEBTACE-sessions, tumor responder-/non-responder, AFP-responder/non-responder) there was no statistical significant difference using the log-rank test (Table I).
Tumor size. Considering the m-RECIST criteria our study showed a significant reduction of size of lesions after first (T1: median 26 mm) and second DEBTACE session (T2: median 21 mm) compared to the baseline (T0: median 64 mm) and between T1 and T2 (Figure 1).
Regarding the EASL-criteria (with T0: median 1733 mm2, T1: median 523 mm2 and T2: median 240 mm2) the difference between T0/T1 and T0/T2 proofed significance, but failed to show significance between T1/T2 Figure 2).
AFP-level. There was a significant (p<0.05) decrease of AFP-levels in the first follow-up examination T1 with a median 26.9 ng/ml compared to T0 with median 31.7 ng/ml. No significant difference was found between T2 with a median 27 ng/ml and T0 as well as between T2 and T1.
In 10 (35.7%) patients the decrease of AFP corresponded with the reduction of the tumor size in imaging; 10 patients were regarded as non-responders according to AFP-levels.
Objective response rate. After the first treatment with DEBTACE, we found a target response in 64.3% (m-RECIST) and 78.5% (EASL) of our patients, respectively. Regarding m-RECIST and EASL-criteria 10 patients (35.7%) and 5 patients (17.9%) showed a stable disease. Based on m-RECIST no progressive disease was observed while 1 patient showed disease progression employing EASL-cirteria. 7 patients showed, in addition to their target lesions, non-target lesions (4 extrahepatic, 3 intrahepatic non-treated lesions) that contributed to the overall response rate. In our cohort of 28 patients the ORR was 15 (53.5%) and 20 (71.4%), respectively when m-RECIST and EASL-criteria were utilized. 4 patients were lost to follow-up.
Survival in subgroups.
Toxicity (CTCAE). During the follow-up period, there were no clinical adverse events exceeding grade 2 considering CTCAE for all patients. In 7 patients, we found a small amount of pleural fluid (grade 1) after DEBTACE, although 4 of these patients already showed pleural fluid before treatment.
Post DEBTACE ascites was found in 10 cases. 5 patients already showed ascites in the baseline examination. In none of these cases paracentesis was required.
Nineteen patients (67.5%) showed symptoms of a postembolisation syndrom (PES) at different levels: 8 patients with an increase of the body temperature above 39°C, 16 patients with abdominal pain, 4 patients with nausea, 11 patients with an increase of bilirubin of 1.5 to 3 times of the standard value. In one case, there was an increase of bilirubin of 3-10 times of the standard value (AE grade 3). Regarding GGT there was an increase of >2.5-5 times (grade 2) in 11 cases, an increase of 5-20 times in 11 cases (grade 3) and an increase of >20 times in 4 cases (grade 4). One of these 4 patients had a slight widening of the bile duct that regressed on its own. In one case, we found a GPT of more than 20 times the standard value. That patient developed a bilioma in the further course. In almost all cases the increases in the laboratory values resolved over time going back to the level prior to DEBTACE.
Considering m-RECIST criteria longest, contrast-uptaking diameter of tumor in mm; T-0: before 1. DEBTACE; T-1: first follow-up after 1. DEBTACE; T-2: after 6 months (median and 75. percentile) *p<0.05 T-0 vs. T-1 und T-2, #p<0.05 T-1 vs. T-2.
Biliary complications. Three patients (10.7%) developed a widening of the bile ducts. 4 patients (14.2%) showed a bilioma without a need for treatment (Figure 3). Two of those 4 patients with bilioma showed also a bile duct widening. In total, we found 7 biliary toxicities in 5 patients. One patient with bile duct stenting developed a cholangitis and consecutive a liver abscess after the second DEBTACE session. Despite intensive antibiotic treatment and CT-guided drainage of the abscess the patient died 106 days after the first DEBTACE treatment.
Discussion
In 2007, 2 clinical studies proved safety and efficacy of drug eluting beads in the transarterial treatment of HCC (5, 6). Further developments of DEB platform extended the release of the drug which lead to less adverse events compared to conventional TACE (7, 8). The beads initially being used ranged from 300-500 μm and 500-700 μm in size, which, compared to smaller sizes like 100-300 μm, proved less efficient and more toxic (9, 10). The drawback of even smaller beads is that they have the ability to reach more distally into arterial branches and cumulate in higher density which causes extensive necrosis in the tumor mass than beads with the size of 100-300 μm that occlude more proximal arteries (10).
In 2011, Namur et al. demonstrated the correlation between the dose of doxorubicin and the area of necrosis surrounding the tumor vessels that could be reached by beads with the size of 100-300 μm (11). Another study from 2011 proved that PVA-particles with a size from 47-90 μm could occlude peritumoral, arterial capillaries and did not enter the sinusoidal space of healthy liver tissue. From there a relative new generation of DEB with a size of 70-150 μm, so called M1®-Beads were increasingly used in the treatment of HCC. Until today there are only a few published clinical trials using M1®-Beads (12-14).
Considering EASL-criteria product of the bi-dimensional, contrast-uptaking diameter of tumor in mm2; T-0: before 1. DEBTACE; T-1: first follow-up after 1. DEBTACE; T-2: after 6 months. (median und 75.percentile) *p<0.05 T-0 vs. T-1 and T-2.
Development of a bilioma after DEB-TACE. Image 1: before DEBTACE; image 2: 2 months after 1. DEBTACE; image 3: 9 months after DEBTACE; image 4: 11 months after DEBTACE; black arrow (image 2-4) indicates a growing bilioma without any clinical symptoms and no abnormalities in the laboratory tests. Therefore no treatment was required.
Compared to one of the first trials using beads (70-150 μm) in 2014 with 45 patients and an ORR of 77.7% (CR 33.3%, PR: 40.4%) referring to m-RECIST after 1 month, we found a comparable ORR (CR+PR) of target lesions referring to EASL of 78.5% (CR: 21.4%, PR: 57.1%) and m-RECIST 64.3% (CR: 21.4%, PR: 42.9%).
The reason for the lower ORR according to m-RECIST could be that our trial also included BCLC-C and a Child-Pugh-B patients compared to Spreafico et al. where only BCLC-A and B-Stage and Child-Pugh-A patients were enrolled (14). However, it is important to note that all BCLC-C patients in our study were allocated to that group because of the impaired ECOG performance status, not because of tumor characteristics or liver dysfunction.
Our ORR of 64.3% is similar to the results of Dekervel et al. with 67.5% but not totally comparable because Dekervel et al. treated 64 patients with beads in the range of 50-100 μm but also in the range of 300-500 μm and 500-700μm (15). Compared to the ORR of other groups e.g. Malagari et al. (68.9%, m-RECIST) or Bhagat (78% of target lesion, EASL) who used beads in the size of 100-300 μm we can report results in the same range (16, 17). Further trials that utilized larger beads (100-300 μm, 300-500 μm, 500-700 μm) showed an ORR after first DEBTACE of 59.5% (EASL) and 51% (m-RECIST), respectively; inferior to our results and those reported by other authors using small sized beads as well (18, 19). This could be an argument in favour for smaller sized beads.
Contrary results have been published by Deipolyi et al., who used M1®-beads as well. In this study CR and PR (m-RECIST) were 16% and 8%, respectively (12). Potential reasons might be that the authors used larger size beads (100-300μm) in addition to beads <150 μm and, even more important, they included far more BCLC-C patients (64%) compared to our cohort including 15.6% of BCLC-C patients. Additionally, because of multifocal disease, they did not administer the beads in a superselective fashion as we did. In our opinion, the superselective catheterisation is crucial for effective treatment and partially explains the differences in the reported results.
In a single case in our study we found disease progression of the target lesion according the EASL-criteria, but not with respect to m-RECIST. The differences and difficulties of SD and PD according EASL and m-RECIST were also discussed in the work of Prajapati et al. (20). The differences are related to the different measurement methods. While measuring the longest diameter of contrast uptaking tumor masses in m-RECIST, EASL uses a product of the diameter and its longest orthogonal axis. In this case, EASL could detect the disease progression earlier than m-RECIST, which showed the progress in the second follow-up examination.
Both methods are predictors for survival. Prajapati et al. even showed a higher correlation for m-RECIST and overall survival than EASL (20).
Earlier trials showed that AFP is a reliable marker to monitor the treatment response and a predictor for survival (17, 19, 21). We can underline this thesis with our results of a significant AFP-decrease in the first follow-up examination. But we have to admit that in the last follow-up examination within the 6 months period there was no significant AFP-decrease with respect to the baseline or the first follow-up parameters. This could be related to progression of the treated tumors of as well as new tumor lesions. In 53.1% of our patients the AFP-level was normal at baseline examination, which shows the low output value that could not fall further. The median baseline value of AFP was 11,1ng/ml in our trial and comparable to others with 16,42 ng/ml (14).
The overall survival in our trial with median 914 days/30.5 months (mean 881 days/29.4 months, standard error 134.8 days) is slightly higher than reported by other trials that used larger beads: e.g. Song et al. with a median OS of 18 months (100-500 μm) (22), Reyes et al. with a median OS of 26 months (100-500μm) (23), Kalva et al. with a median OS of 14,7 months (300-500 μm) (24) and Dekervel et al. with median OS of 20.5 months (50-100μm and additional larger beads) (15). Burrel et al. showed results with a superior OS of 48.6 months, but included in his study only BCLC-A and B patients (25). In other trials that included the BCLC-C patients as well the median OS was 13.5 months and 13.3 months (26, 27).
The median OS in our subgroup analysis was 20.5, 26.8 and 7.6 months for BCLC-A, -B and -C patients, respectively. The OS in BCLC-A and B are in well alignment to the data published by Dekervel et al. (BCLC-A 24 months, BCLC-B 20.3 months). There is a difference regarding the BCLC-C overall survival data of Dekervel et al. 15.5 months, OS in this subgroup could be contributed to the good performance status and the mean age of 62 years of their cohort (15). All our BCLC-C patients had an ECOG performance status of 1 and a mean age of 76.5 years.
We did not find a significant difference regarding OS in our subgroup analysis with respect to the BCLC system. One possible explanation could be the BCLC-system itself. In that widely accepted staging and treatment system it is not only the tumor burden that determines the stage of the disease but also the ECOG performance status, that could easily down-stage a patient e.g. from BCLC-B to C, although, in fact, he has only little tumor burden with good treatment options. This problem was already addressed in the BRIDGE-trial, which demonstrated a surprisingly high rate of liver transplantations in BCLC-D patients. According to the BCLC-D stage only these patients must have been allocated to ”best supportive care“ only. The BCLC-D stage was caused by the ECOG-score only, however, since all patients fulfilled the milan-criteria they were treated accordingly (28).
In our study PFS for target lesions was 14.2 months (m-RECIST and EASL) and similar to the results of Reyes et al. (13 months), but superior compared to Kalva et al. with a PFS of 5.1 months in BCLC-C patients (26).
Compared to conventional, lipiodol-based TACE the dose of doxorubicin in the peripheral blood is significantly reduced after DEBTACE (5). With smaller bead sizes other trials could show a reduction of the postembolisation syndrome (6, 8, 18, 29). For this reason, we expected a decrease of PES using M1®-beads. At least one symptom of PES grade 1-2 like abdominal pain, fever or nausea occurred in 67.5% of our patients during the first 3 days after treatment. 28.6% had fever, 57.1% complained about abdominal pain and 10.7% had nausea. These results are similar to the trial of Odisio et al. Using M1®-beads they found an incidence of 67.5% of PES grade 1-2 (fever 25%, 46.5% pain, 23.3% nausea) (13). Spreafico et al. treated 45% of patients in his cohort with M1®-beads and had noticeably less PES (fever 2.2%, pain 4.4%, nausea 2.2%) in this aforementioned group, which included predominantly patients with Child-Pugh-A cirrhosis and no BCLC-C patients (14). Other trials did not show differences in the occurrence of PES comparing M1®-beads combined with larger beads or larger beads only (12, 30). But both trials did not treat with M1®-beads only. In comparison of treatments with bead sizes of 100-300 μm and 300-500 μm these trials showed a reduction of PES in favour of the smaller bead sizes.
In our trial, there were no systemic adverse events. In 2 cases, there were grade 4 AE with a rise of GGT and 3 AEs grade 3. Furthermore, we did not observe a significant difference in blood results like GOT, GPT and GGT compared to baseline parameters, which indicated reduced tissue damage due to superselective embolisation and deeper penetration of the beads into the tumor. In concordance with other published data we can confirm a general, transient increase of liver enzymes, bilirubin and GGT after DEBTACE, which usually decreases shortly after the procedure (8, 17, 31, 32).
Biliary complications like the dilation of the bile duct, which occurred in 3 of our patients (10.7%), and the development of a bilioma in 4 patients (14.7%) (2 patients had a dilation of the bile duct and a bilioma) were rare but serious adverse events. Liver cirrhosis with a hypertrophy of the peribiliary plexus is considered as a protective factor for the development of a bilioma (33, 34). That could be an explanation for the higher rate of biliary complications (29.7%) in a trial using M1®-beads in HCC and liver metastases (13).
The discussion of the increased biliary toxicity using smaller beads is equivocal. There are authors that consider smaller beads as less toxic; others consider them more toxic by causing more adverse events (9, 10, 12, 17, 30, 34, 35). Beads with smaller diameters have the ability to reach more distal arteries and could therefore deliver more drugs to a territory because of the relatively higher surface, which results in an extended tumor necrosis but could also injure healthy liver tissue. Especially beads with the size of 40-60μm can harm the peribiliary plexus with its only arterial blood supply and cause a bile duct necrosis. That is considered as a reason for the development of biliomas. Bhagat et al. reports of an incidence of biliomas in 54% of his patients, which is considerably higher compared to our results (16). The authors explained it with the larger bead sizes (100-300μm) and different tumor entities like metastases from neuroendocrine tumors, which don't have the “protective effect” of the liver cirrhosis. Odisio et al. did not report a difference in the appearance of biliomas in patients with HCC or liver metastasis using M1®-beads, but they had a relatively few patients with liver cirrhosis (68%) compared to other studies (13). In our analysis, all patients suffered from liver cirrhosis, which could have served as a protective factor against the development of biliomas.
Furthermore, we used a superselective approach in most of the cases and in 59% of our patients larger or multifocal disease was noted which is also considered as a protective factor against the development of biliomas.
The incidence of liver abscesses after DEBTACE is reported around 0.26-3.12% with a mortality of 20-100% (5). The incidence rises in the presence of a failure of the sphincter oddi, a pappilotomy or a bilodigestive anastomosis with ascending bacteria to 20-80%. We had a single case (3.6%) with a liver abscess following DEBTACE. This patient already had a stent in the bile duct before he was treated with DEBTACE. Ascending bacteria caused a cholecystitis, a bilioma and finally an abscess formation, which was drained in the course of the disease. Unfortunately, this patient died 106 days after his first treatment with DEBTACE.
Other trials confirm the risk of liver necrosis/abscess development in the presence of a dysfunction of the biliary system (36). There was no 30-day mortality observed in our trial.
Conclusion
By using DEBTACE with microspheres <150 μm, we demonstrated a significant decrease of the contrast up-taking tumor tissue and the AFP-value. The results for ORR and OS are another argument for the effectivity of drug-eluting M1®-beads. Especially the superselective administration of the M1®-beads seems to have impact on the reduction of hepatobiliary toxicity and the loss of systemic adverse events.
Limitations were the retrospective design, the small number of cases, the missing of a long-term-follow-up and a peer group with larger bead sizes.
Further trials e.g. the “Doxorubicin-eluting LC Bead M1 for Patients with Hepatocellular Carcinoma (DEBDOX)” are necessary to evaluate the efficacy and toxicity of DEBTACE with M1®-beads.
Footnotes
Conflicts of Interest
Jakobs T. received financial support for attending and speaking at symposia and congresses and has a position on an advisory board. All other authors declare not to have conflicts of interest.
- Received August 29, 2017.
- Revision received October 10, 2017.
- Accepted October 13, 2017.
- Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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