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Selective internal radiation therapy (SIRT) before partial hepatectomy or radiofrequency destruction for treatment of hepatocellular carcinoma in cirrhotic patients: a feasibility and safety pilot study
Abdominal Surgery, Hôpital Erasme, Université Libre de Bruxelles, BelgiumCentre de Chirurgie Hépato-Biliaire de l'ULB, Université Libre de Bruxelles, Belgium
Abdominal Surgery, Hôpital Erasme, Université Libre de Bruxelles, BelgiumCentre de Chirurgie Hépato-Biliaire de l'ULB, Université Libre de Bruxelles, Belgium
Centre de Chirurgie Hépato-Biliaire de l'ULB, Université Libre de Bruxelles, BelgiumRadiology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium
Centre de Chirurgie Hépato-Biliaire de l'ULB, Université Libre de Bruxelles, BelgiumDigestive Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium
Surgery, Institut Jules Bordet, Université Libre de Bruxelles, BelgiumCentre de Chirurgie Hépato-Biliaire de l'ULB, Université Libre de Bruxelles, Belgium
Preoperative selective internal radiation therapy (SIRT) may improve the results of partial hepatectomy (PH) or radiofrequency destruction (RF) for hepatocellular carcinoma (HCC) in patients with cirrhosis. The aim of this study was to evaluate the feasibility and safety of this combined approach.
Methods
Patients with cirrhosis and HCC selected for PH or RF were prospectively included and systematically proposed for preoperative SIRT. Feasibility and safety of SIRT and post-SIRT PH or RF were assessed.
Results
Thirty patients were included. SIRT was contraindicated in seven, due to lack of access to tumour artery or to hepato-pulmonary shunts. SIRT was performed in 23 patients without significant complications. Post-SIRT, surgery was refuted in seven patients, due to tumour progression or the patient's deteriorating condition. After surgery, major complications were observed in 2/16 patients (12.5%) and one patient died 52 days post-surgery. A major tumour pathological response was seen in most patients who underwent surgery after SIRT.
Conclusions
On intention-to-treat basis, the overall feasibility of combining preoperative SIRT and surgery was limited. Preoperative SIRT did not increase expected operative morbidity, but post-SIRT, a third of patients were refuted for surgery. Accurate selection criteria and potential long-term oncological benefit of this approach remains to be determined.
ClinicalTrials.gov NCT01686880.
Introduction
Partial hepatectomy (PH) and in situ tumour destruction with radiofrequency (RF) are the first treatment options to consider for patients with hepatocellular carcinoma (HCC) and compensated cirrhosis who are not candidates for liver transplantation,
The feasibility and efficacy of these tumour-directed approaches is, however, dramatically limited by the underlying liver disease, the need to preserve sufficient non-tumour remnant liver, and high tumour recurrence rates. No neoadjuvant or adjuvant treatments have been shown to improve long-term outcomes in patients with HCC when used in association with PH or RF. In particular, neither preoperative locoregional therapy with transarterial chemoembolisation (TACE) nor adjuvant treatment with sorafenib have shown a significant clinical benefit.
Selective internal radiation therapy (SIRT), which relies on the intra-hepatic arterial injection of yttrium 90 (90Y)-labelled microspheres, has recently been established as an effective treatment for liver tumours. In HCC, SIRT is effective as palliative therapy in patients who are not candidates for curative-intent therapies or as a bridge before liver transplantation.
Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.
Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.
Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.
The Post-SIR-Spheres Surgery Study (P4S): retrospective analysis of safety following hepatic resection or transplantation in patients previously treated with selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres.
Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.
In addition, lobar or segmental 90Y injection (described as radiation lobectomy/segmentectomy), may promote atrophy of the embolised sector and a compensatory hypertrophy of the contralateral liver, allowing surgical resection in cases of initially insufficient future liver remnant (FLR).
Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections.
Volumetric changes after (90)y radioembolization for hepatocellular carcinoma in cirrhosis: an option to portal vein embolization in a preoperative setting?.
On the basis of such findings, it was hypothesized that preoperative SIRT may improve the overall results of partial hepatectomy or RF in the treatment of HCC, leading to improved efficacy of local resection or destruction and, potentially, to better long-term tumour control. Currently, the overall feasibility and safety of this combined approach has not been explored on an intent-to-treat basis in a therapeutic management plan from a multidisciplinary tumour board following a diagnosis of HCC. We report the results of a prospective series in which SIRT was systematically proposed as a preoperative treatment in patients with HCC and cirrhosis selected for PH or RF. The end points of this exploratory study were the feasibility and safety of the combination.
Methods
The study was conducted at 2 centers in Belgium between March 2009 and September 2016. The study received Institutional Review Board approval and patients were included after written informed consent had been obtained (NCT01686880).
Patients
During the study period, all patients selected for PH or RF for HCC at the participating centers were considered for inclusion in this prospective non-randomized study. Each patient's records were discussed in multidisciplinary tumour board meetings which included members of the liver transplant team. The diagnosis of HCC was made in nodules ≥20 mm displaying arterial wash-in and portal wash-out on contrast-enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI) and in nodules <20 mm with the same imaging characteristics and associated with elevated alpha-fetoprotein (AFP). The diagnosis of HCC was confirmed by pathological examination of the resected liver tissue or on pre-RF tumour biopsy. PH or RF was proposed after multidisciplinary assessment of the operability, in the absence of unresectable extrahepatic dissemination, macrovascular invasion, or significant portal hypertension defined as a portosystemic gradient ≤10 mm Hg.After inclusion, patients underwent a simulation procedure to evaluate the feasibility of SIRT.
SIRT simulation
A supraselective simulation of tumour-containing liver segments or lobe was performed to assess the feasibility of SIRT. Initially, a contrast-enhanced angio-CT scan was performed with early and late arterial phases in order to determine the optimal catheter position for simulation and therapy. After supraselective catheterisation of the tumour-feeding segmental or lobar artery and placement of the catheter into the treatment position, a tracer dose (148 MBq) of technetium-99 (99Tc)-labelled macro aggregated albumin (MAA) was injected. The patient was transferred to the Nuclear Medicine Department for single positron emitting computed tomography coupled with CT scan (SPECT-CT) imaging of the lungs, liver, and abdomen. This simulation phase aimed to assess the feasibility (coverage and uptake of the lesion(s) to be treated) and safety (the absence of significant pulmonary or gastrointestinal dissemination seen on the MAA SPECT-CT images) of SIRT. The study's safety requirements defined a 10% maximum accepted limit for pulmonary shunting (lower than in the package insert of the device which recommends a dose reduction in patients with pulmonary shunting between 10% and 20%).
If there was no contraindication to SIRT, therapeutic activity and radiation dose of 90Y were calculated in order to achieve a (ablative) dose >70 Gy in the normal liver parenchyma surrounding the tumour. If SIRT was not indicated for technical reasons, patients continued on to surgery, either PH or RFA, without preoperative treatment. These patients were considered as internal controls.
SIRT procedure
Several days after SIRT simulation, intra-arterial 90Y resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) were injected supraselectively into the position defined during SIRT simulation. All patients received morphine analogues and anti-emetic medications during 90Y microspheres injection. On the first day after SIRT, 90Y PET-CT was performed to verify the deposition of the radioactive microspheres within and outside the liver. Patients were hospitalized for 24 h for observation and were prescribed a 3-day course of corticosteroids and a 4-week course of proton-pump inhibitors (PPI) for gastric protection.
Post-SIRT evaluation
Patients were clinically reassessed in outpatient clinics, at 2 and 4 weeks after SIRT, and before surgery. Patients we reassessed at 2 and 4 weeks after SIRT, and before surgery, including clinical examination, laboratory and imaging, either CT or MRI. Post-SIRT events were recorded prospectively.
Surgery
PH or RF was planned at least 6 weeks after SIRT at the discretion of the multidisciplinary treatment group. This period has been decided for radioprotection safety reasons. As the patients included were initially candidate for surgical treatment, the time before surgery was kept relatively short to limit the risk of drop-out in case of non-response and tumour progression.
For patients in whom SIRT was not feasible, surgery was performed soon after the simulation procedure. PH was preferentially proposed for peripheral HCC and when tumour size was >30 mm. RF was preferentially proposed for tumours ≤30 mm, that were centrally located and at distance from major vessels, and when surgery would require a major hepatectomy. PH was performed via laparoscopic or open approach according to technical considerations and surgeon's choice. All resections were performed under intraoperative ultrasound (IOUS) guidance with the aim of achieving a tumour-free margin. Major resection was defined as the resection of ≥3 liver segments. RF was performed preferentially via a laparoscopic approach or via an open approach when required for access reasons, under IOUS guidance using Radiotherapeutics (Boston Scientific) or Cool-Tip™ RF System (Covidien) devices. Completeness of RF treatment was verified with IOUS by the creation of a hyperchogenic zone covering the entire initial tumour volume.
Post-surgical evaluation
After PH or RF, operative complications were defined as all events occurring within 90 days, during the same hospital stay or requiring re-hospitalization. Operative complications were graded according to the Clavien-Dindo classification.
Minor and major complications were defined by Clavien-Dindo grades <3 and ≥ 3, respectively. Operative complications were recorded in two groups of patients: patients in whom SIRT was feasible before surgery (SIRT+Surg+) and patients in whom SIRT was not feasible and who underwent PH or RF without preoperative treatment (Surg+).
Pathological response
Resected specimens in patients undergoing PH were analysed for pathological response. Tumour necrosis and fibrosis were analysed using haematoxylin eosin techniques. Major pathological response was defined when tumour necrosis was ≥50% and complete pathological response (CPR) by the absence of residual cancer cells.
Survival
This study was not designed to evaluate the effect on survival, but for descriptive purposes, overall survival (OS) was defined as the time from surgery to last follow-up or death and disease-free survival (DFS) time was defined as the time from surgery to disease recurrence or progression (at any site) were recorded for descriptive purposes. The time and site of recurrence were captured on the report forms. OS on intention to treat (ITT) analysis was defined as the time from SIRT simulation to last follow-up or death.
Results
Patients
Thirty patients were included after multidisciplinary discussion and exclusion of patients eligible for liver transplant. Patient and baseline tumour characteristics are described in Table 1. The most common causes of liver disease were alcohol use and hepatitis B or C virus infection. All patients had compensated Child-Pugh A cirrhosis. Most patients (24 of 30) had Barcelona Clinic Liver Cancer (BCLC) stage A. Eight patients had received treatment for HCC before inclusion in the study (Table 1);
Table 1Baseline patient and tumour characteristics
Characteristic
Study population (n = 30)
Median age (range)
65 (26–78)
Gender (M/F)
23/7
Etiology of liver disease
Alcohol use
10
Hepatitis C virus
9
Hepatitis B virus
7
NASH
1
Haemochromatosis
1
Other
2
Median Child Pugh score (range)
5 (5–7)
Median MELD score (range)
8 (6–11)
BCLC stage
0
0
A
24
A1
18
A2
4
A3
0
A4
2
B
5
C
1
Number of tumours
1
19
2–3
9
>3
2
Median tumour size (mm) (range)
38 (16–160)
Median AFP level (ng/ml) (range)
16.9 (2.1–121000)
Previous treatment for SIRT
8
Partial hepatectomy
2
RF
1
TACE
4
Sorafenib
1
NASH: non-alcoholic steato-hepatitis, MELD: model for end-stage liver disease, BCLC: Barcelona Clinic Liver Cancer, AFP: alpha-fetoprotein.
SIRT was deemed to be unsuitable for seven patients following the simulation procedure. In three patients, it was not possible to supraselectively catheterise the tumour artery, and for one patient there was a technical failure in catheterisation of the hepatic artery (Fig. 1). Three patients showed hepato-pulmonary arterio-venous shunting >10% (10%, 12.5%, and 15% lung deposition of 99Tc-MAA). All these seven patients underwent PH or RF without preoperative treatment. Twenty-three patients received SIRT as a preoperative treatment (Table 2). The median total activity delivered was 0.95 GBq to a median tumour volume of 32.3 ml.
Figure 1Patient flow chart. aContraindications for SIRT: not possible to selectively catheterise the tumour artery (n = 3), pulmonary shunt >10% (n = 3), not possible to catheterise the hepatic artery (n = 1). bContraindications for surgery post-SIRT: tumour progression (n = 3), new comorbidities (n = 2), transient liver failure (n = 1), lost to follow-up (n = 1)
Following SIRT, two patients (8.7%) developed gastrointestinal ulcer requiring increased PPI doses, and one patient (4.3%) experienced transient ascites without other sign of liver failure. Minor complications were observed in six patients (26%), comprising nausea, pain, or fever. At the preoperative reassessment, among the 23 patients who received SIRT before surgery, 12 presented a radiological response to SIRT according to mRECIST criteria, including complete response in 5. A stable radiological disease was observed in 9 other patients and 2 patients progressed as a new lesion appeared. In the 23 patients receiving SIRT, 10 had elevated AFP at baseline. After SIRT (4 to 6 weeks), a significant decrease in AFP was observed in 5 cases, an increase in 2 and no change in 3. In 20 out of the 23 patients who received SIRT, no modification of the Child Pugh and MELD scores was observed as compared with pre-SIRT evaluations. Three patients presented a deterioration of the liver function after SIRT, as indicated by an increase of the MELD score from 9 to 13, 12 to 16 and 7 to 15, corresponding to no change of the Child Pugh score in the first case, an increase from 7 to 9 points in the second and from 5 to 7 in the third. Of note, this last patient received additional portal vein embolization in preparation of a right hepatectomy.
Re-evaluation following SIRT found that surgery was no longer indicated for seven patients (Fig. 1). This was due to tumour progression in three patients, appearance of new liver-related comorbidities in two patients, reversible liver failure after portal vein embolization 12 weeks after SIRT in one patient, and loss of follow-up in one patient. All three patients with tumour progression after SIRT had FDG-PET scan positive tumours at baseline, two patients had tumours >30 mm, two had multiple tumours, and two had elevated AFP. In these three patients, tumour progression was observed in the SIRT-targeted lesion and was associated with pulmonary metastasis in one patient and with a new liver tumour in another. These patients died from tumour progression 4, 15, and 15 months post-SIRT.
Surgery
Of the 23 patients undergoing PH or RF, 16 patients received preoperative SIRT (SIRT+Surg+) and seven patients received no SIRT. The median interval between SIRT and surgery was 102 days (range 54–235 days). The surgical procedures and postoperative outcomes in patients who underwent surgery are detailed in Table 3. Of the 16 patients who had a PH, five underwent a major resection. Four patients with multiple tumours underwent both PH and RF. No major intraoperative differences were observed between the SIRT+Surg+ group and the Surg+ group (Table 3). However, there appeared to be a tendency toward higher blood loss and a higher requirement for blood transfusions in the SIRT+Surg+ patients. Macroscopic liver structure and volume changes were observed in some patients after lobar SIRT treatment, however, no unusual surgical difficulties were experienced in these patients.
Table 3Operative and postoperative data in patients who underwent surgery with and without preoperative SIRT
SIRT+Surg+ (N = 16)
Surg+ (N = 7)
Type of surgery
RF
5
2
PH
9
3
RF + PH
2
2
Minor resection
7
4
Major resection
4
1
Open approach
11
4
Laparoscopic approach
4
1
Mean duration of surgery (min) (range)
164 (90–280)
165 (60–288)
Blood loss, ml) (range)
800 (0–4000)
475 (0–2400)
Number of Pringle manoeuvre
6
3
Intraoperative blood transfusion (number of patients)
4
1
Operative complications according to Clavien-Dindo classification (n, %)
0
5
4
I
1
0
II
7)
1
III
2
2
IV
0
0
V
1
0
No or Minor complications (n, %)
13
5
Major complications (n, %)
3
2
Median duration of hospital stay (days) (range)
8 (5–15)
10 (3–16)
Readmission (n)
4
0
SIRT+Surg+, patients who received SIRT prior to surgery; Surg+, patients who did not receive SIRT prior to surgery; RF, radiofrequency; PH, partial hepatectomy.
After surgery, major operative complications were observed in two of 16 patients in the SIRT+Surg+ group (Table 3). One patient who underwent right hepatectomy died at home on postoperative day 52, after a postoperative stay of 8 days. Physical examination and blood liver tests were normal at the first postoperative visit 32 days post-surgery. The cause of death is unknown. Postoperative outcome appeared similar in the seven patients in the Surg+ group (Table 3).
Pathological response
Pathological response was analysed on resected specimens for the patients who underwent PH. After SIRT, a major pathological response was observed in eight of the 10 resected patients in the SIRT+Surg+ group, including CPR in four patients. In comparison, in the five patients in the Surg+ group who underwent PH, no tumour necrosis was observed in three specimens and minimal necrosis (<10%) in two.
Survival
In the whole population of patients who received surgery (n = 23), the median follow-up was 24.6 months, ranging from 3 to 78 months. In the SIRT+Surg+ and Surg+ groups, median OS was 25 and 24 months, respectively, and median DFS was 11 and 12 months, respectively. Median times to recurrence were 13.8 and 11 months in the SIRT+Surg+ and Surg+ groups, respectively. Eleven patients in the SIRT+Surg+ group and six in the Surg+ group had recurrence of intrahepatic tumours. One patient in the SIRT+Surg+ group developed extrahepatic metastases. Four patients in the SIRT+Surg+ group remained disease-free 3, 25, 29, and 35 months after surgery and one patient in the Surg+ group was disease-free after 26 months of follow-up. On ITT analysis, the median OS in the whole population, in the SIRT+Surg+, SIRT+Surg-, and SIRT-Surg+ were respectively of 27, 26, 16 and 28 months.
Discussion
The treatment of HCC in patients with cirrhosis remains a complex problem. The best therapeutic choice for the individual patient among the therapeutic options available is dependent on multiple factors including the tumour stage and location, the stage of cirrhosis, the presence of cirrhosis-related comorbidities, and access to or contraindications to liver transplantation.
The increasing incidence of HCC and organ shortage for liver transplantation, suggest that liver-directed approaches, including PH, RF and intra-arterial locoregional therapies, will probably have an important role in the future for palliative and curative-intent treatment for selected patients. However, the impact of these treatments on long-term outcomes remains unclear. Outcomes for PH and RF remain poor, with high morbidity and tumour recurrence rates, and in those cases of prolonged survival and occasionally cures there are currently no reliable predictive factors.
The rationale for using SIRT as a preoperative treatment before PH or RF is based on several factors. Firstly, there is evidence that SIRT is an effective treatment for HCC. For example, a randomized study in patients with unresectable HCC showed superior tumour control with SIRT compared with TACE, suggesting that SIRT is a potential locoregional therapy in the multimodal management of HCC.
Thus, every combined approaches using SIRT as first-line treatment may ensure that patients will receive an effective treatment, independently of the feasibility of the following therapeutic steps. Secondly, SIRT may produce significant tumour downsizing, potentially improving the safety and efficacy of subsequent PH or RF, allowing parenchyma-preserving resection of initially unresectable tumours. Finally, as reported for TACE,
Prognostic relevance of objective response according to EASL criteria and mRECIST criteria in hepatocellular carcinoma patients treated with loco-regional therapies: a literature-based meta-analysis.
it might be expected that the outcome after SIRT could serve as a predictive factor for assessment of surgical risk and benefit. More precisely, the tolerability of SIRT could estimate the functional liver reserve and the safety of subsequent PH or RF.
This study was designed to assess the feasibility and the safety of a combined therapeutic approach using SIRT before PH or RF for treatment of HCC in patients with cirrhosis. First, the feasibility of this approach appears limited as only 16/30 patients (53%) received SIRT and underwent PH or RF. The main reasons that SIRT was contraindicated were the absence of a specific supraselective arterial supply to the tumour, and extrahepatic dissemination of the microspheres, mainly shunts to the lungs. The absence of a selective tumour artery is an intrinsic limitation for all intra-arterial therapies. However, in the SIRT procedure, the MAA simulation step allows clinicians and patients to avoid ineffective and potentially toxic treatment without precluding a rapid redirection of the patient to PH or RF if appropriate. In this study a limit of 10% for lung deposition was chosen, this was below the 20% limit that is commonly accepted. If a limit of 20% had been applied in this series, all patients excluded for this reason would have been accepted for SIRT. A major concern using this 2-step approach is that first-line SIRT therapy may eventually result in further contraindication for surgery. In this series, of 23 patients who were initially candidates for PH or RF, seven were no longer indicated for surgical treatment after SIRT. In three of these seven patients, surgery was not indicated due to intra-hepatic tumour progression. While the delay between SIRT and re-evaluation for surgery was relatively short, it cannot be excluded that this waiting period was responsible for tumour progression. This underlines the need to define the optimal timing in such neoadjuvant strategy. In the present work, the aim of preoperative SIRT was not to modulate the liver volumes, and thus the period between SIRT and surgery was kept relatively short, inferior to the 6 to 9 months required to obtain the atrophy of the embolized liver and the regeneration of the contralateral liver (25). While a greater delay may improve the response, we intent to limit the interval period of time before surgery to reduce the risk for tumour progression in case of non-response to SIRT that may preclude the chance for further surgical treatment. This also stresses the need for further studies to determine the best method for early assessment of the tumour response after SIRT.
However, these patients could have aggressive tumours in which surgery would have had a minimal impact for long-term tumour control. Interestingly, all three patients with progressive disease after SIRT had FDG-PET positive tumours at initial work-up, a factor that has been correlated with poor prognosis and poor response to intra-arterial therapies in HCC.
[18F]fludeoxyglucose positron emission tomography and computed tomography as a prognostic tool before liver transplantation, resection, and loco-ablative therapies for hepatocellular carcinoma.
Prognostic significance of (1)(8)F-FDG uptake in hepatocellular carcinoma treated with transarterial chemoembolization or concurrent chemoradiotherapy: a multicenter retrospective cohort study.
Three other patients did not receive surgery after SIRT due to new liver-related comorbidities in two patients and transient liver failure after portal vein embolisation in one. These six patients initially selected for PH or RFA but excluded after SIRT, illustrate a potential major drawback of this strategy as it may represent the loss of an opportunity for curative-intent treatment. However, these observations also suggest that both the tumour response and the tolerance to SIRT could represent additional selection criteria for subsequent surgical treatment, leading to the exclusion of patients with poor oncologic prognosis or insufficient liver reserve.
In terms of safety, SIRT did not appear to markedly affect morbidity following subsequent PH or RF, as complications rates in these patients were similar to those reported in the literature in patients with cirrhosis that underwent surgery for HCC without preoperative treatment.
Moreover, no major differences were observed in the postoperative outcome between the SIRT+Surg+ and the Surg+ groups. No specific intraoperative problems in SIRT+Surg+ patients, such as adhesions due to radiation as previously described,
There was a tendency to higher blood loss after SIRT and higher transfusion requirements; these could be related to structural macroscopic liver changes observed in some patients after lobar SIRT.
This study was not powered to analyse the efficacy of this therapeutic combination and the effect on survival could not be evaluated. Notably however, a major pathological response was observed in most patients in whom the tumour was resected after radioembolisation, including CPR in four patients. Interestingly, although follow-up was quite short, the four patients with CPR to SIRT were alive without recurrence, 35, 28, 24, and 3 months post-surgery.
In conclusion, the combination of preoperative SIRT and surgery is well tolerated for treatment of HCC in patients with cirrhosis, but may not be feasible for a high proportion of patients for technical or clinical reasons. This underlines the need to better determine selection criteria to identify the patients for whom this sequential treatment may be appropriate. The potential clinical benefits of this new therapeutic strategy should be further evaluated in randomised studies with long-term analysis.
Funding
This work was supported by a grant from Sirtex Medical Ltd.
Conflicts of interest
None.
Acknowledgments
We would like to acknowledge the contribution of medical writers, Sandy Field, PhD, and Tim Latham BSc of ESP Bioscience Ltd for editing of this manuscript.
References
European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer
EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma.
Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.
Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.
Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.
The Post-SIR-Spheres Surgery Study (P4S): retrospective analysis of safety following hepatic resection or transplantation in patients previously treated with selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres.
Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections.
Volumetric changes after (90)y radioembolization for hepatocellular carcinoma in cirrhosis: an option to portal vein embolization in a preoperative setting?.
Prognostic relevance of objective response according to EASL criteria and mRECIST criteria in hepatocellular carcinoma patients treated with loco-regional therapies: a literature-based meta-analysis.
[18F]fludeoxyglucose positron emission tomography and computed tomography as a prognostic tool before liver transplantation, resection, and loco-ablative therapies for hepatocellular carcinoma.
Prognostic significance of (1)(8)F-FDG uptake in hepatocellular carcinoma treated with transarterial chemoembolization or concurrent chemoradiotherapy: a multicenter retrospective cohort study.
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