Research Article
Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis

https://doi.org/10.1016/j.jhep.2017.02.022Get rights and content

Background & Aims

There is limited information on the use of stereotactic body radiotherapy (SBRT) as a bridge to liver transplantation for hepatocellular carcinoma and no study comparing its efficacy to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). We aimed to ascertain the safety and efficacy of SBRT on an intention-to-treat basis compared with TACE and RFA as a bridge to liver transplantation in a large cohort of patients with hepatocellular carcinoma.

Methods

Outcomes between groups were compared from the time of listing and from the time of transplant. Between July 2004 and December 2014, 379 patients were treated with either SBRT (n = 36, SBRT group), TACE (n = 99, TACE group) or RFA (n = 244, RFA group).

Results

The drop-out rate was similar between groups (16.7% SBRT group vs. 20.2% TACE group and 16.8% RFA group, p = 0.7); 30 patients were transplanted in the SBRT group, 79 in the TACE group and 203 in the RFA group. Postoperative complications were similar between groups. Patients in the RFA group had more tumor necrosis in the explant. The 1-, 3- and 5-year actuarial patient survival from the time of listing was 83%, 61% and 61% in the SBRT group vs. 86%, 61% and 56% in the TACE group, and 86%, 72% and 61% in the RFA group, p = 0.4. The 1-, 3- and 5-year survival from the time of transplant was 83%, 75% and 75% in the SBRT group vs. 96%, 75% and 69% in the TACE group, and 95%, 81% and 73% in the RFA group, p = 0.7.

Conclusions

In conclusion, SBRT can be safely utilized as a bridge to LT in patients with HCC, as an alternative to conventional bridging therapies.

Lay summary

Patients with liver cancer included in the waiting list for liver transplantation are at risk of tumor progression and death. Stereotactic body radiotherapy may be a good alternative to conventional therapies to reduce this risk.

Introduction

Liver transplantation (LT) represents the best treatment option for patients with selected hepatocellular carcinoma (HCC) but due to organ shortage most regions place limits on the size and number of tumors that qualify for this therapy. The best methods to prevent drop-out from the waiting list due to tumor progression and/or to reduce post-transplant tumor recurrence are unknown [1]. According to the American Association for the Study of Liver Diseases guidelines for the management of HCC, bridging therapies should be applied if the expected waiting time is longer than 6 months [2]. In practice, as it is often difficult to predict the length of time a patient may wait, thus many centers will provide bridging therapies once the patient is listed.

Local HCC treatment as a “bridge” to LT is utilized in many institutions in order to minimize tumor progression while the patient is waiting for an available graft [3] and to potential reduce post-transplant recurrence rates [4]. Transarterial chemoembolization (TACE) and ablation techniques (radiofrequency ablation [RFA], microwave ablation or percutaneous ethanol injection) are the most common techniques used as bridging therapies. These therapies can have a deleterious impact on liver function and are generally only recommended for patients with well-compensated cirrhosis [5].

Stereotactic body radiation (SBRT) is a more recent and effective treatment for early and advanced stage HCC [6], [7], [8]. There are relatively few reports of SBRT for HCC bridging therapy and no studies comparing its effectiveness as bridging therapy with other forms of treatment. We have previously reported on a cohort of ten patients with HCC treated with SBRT safely [9]. Others have reported similar results in the transplant setting [10], [11]. The aim of this study was to ascertain the safety and efficacy of SBRT on an intention-to-treat (ITT) basis compared with TACE and RFA as a bridge to LT in a large cohort of patients with HCC.

Section snippets

Study design

All patients listed for LT with a diagnosis of HCC at the University Health Network between July 2004 (the date of the first use of SBRT as a bridge to transplant at our institution) and December 2014, who received a bridging therapy were identified as potential candidates for this study. Patients that were treated either with SBRT (SBRT Group), TACE (TACE group) or RFA (RFA group) as bridging therapies were compared. Those patients that received treatment with SBRT after TACE or RFA failure

Results

From July 2004 to December 2014, 594 patients were listed at Toronto General Hospital with a preoperative diagnosis of HCC. Of these, 406/594 (68%) received bridging therapies. The majority of patients 244/406 (60.1%) were bridged with RFA, while 99/406 (24.4%) received TACE and 36/406 (8.9%) were bridged with SBRT; the remaining patients (n = 27) received either other treatments or were bridged following recurrence after liver resection. The distribution of patients is summarized in Fig. 1. The

Discussion

This is the first study to show that SBRT may be as effective and safe as TACE or RFA when used to maintain the candidacy of patients with HCC on the wait list for LT. The overall survival after LT is also similar with these techniques.

Stereotactic body radiation therapy (or SBRT) is an external beam radiation therapy method that precisely delivers a high dose of radiation to an extracranial target using either a single dose or a small number of high dose fractions. In general, radiation

Financial support

No financial support was received in relation to this manuscript.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Authors’ contributions

GS, AB, MD, LAD & DRG: Designed the study and wrote the manuscript; MR and RR: Assisted with data collection; SF: Re-reviewed all the pathology specimens; NG & RB: Assisted in the statistical analysis and critical appraisal; AG, PDG, JK, MB & JB: Assisted in writing the manuscript and provided a critical review.

Acknowledgments

We would like to acknowledge Dr. Pablo Munoz and Ramjar Rajakumar for their assistance in data collection.

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